On the early evolutionary stage of the geosphere and biosphere and the problem of early glaciations

The early evolutionary stages of the geosphere and biosphere are determined by three interrelated factors: (1) continuous cooling of the surface and interior (mantle) of the Earth (the mean temperatures of the mantle and surface decreased by a factor of 1.5–2 and 3–4, respectively; the mean heat flow was reduced by approximately one order of magnitude, and viscosity, by three orders); (2) continuous stepwise oxidation of the surface, which was particularly well pronounced from 3.8 to 1.8 Ga; and (3) periodic and correlated fluctuations of conditions in the geosphere and biosphere of varying extent and nature. The major boundaries of this evolution were about 4 Ga (the origin of rather thick and heterogeneous earth’s crust, the origin of life); about 3 Ga (appearance of a strong magnetic field, an increase in photosynthetic activity); about 1.8–1.9 Ga (appearance of an oxidized atmosphere, the first supercontinent, possibly, the first superplumes from the nucleus); and about 0.75 Ga (acceleration of subduction, “watering” of the upper mantle, elevation of continents with vast land masses, shelves, large rivers, and the first great glaciations). The significance and correlations of the earliest events (before and about 4 Ga) and events about 750 Ma are widely debated. In the Late Archean and Early Proterozoic (before 1.8 Ga), the biosphere was dominated by cyanobacteria, the dynamics and developmental peaks of which are marked by the presence of widespread stromatolite buildups in carbonaceous rocks (initially, mostly dolomitic matter). About 700–750 Ma, intense and frequent glaciations developed, marking the cooling of the Earth. The greatest glaciation apparently occurred about 640 Ma, which gave rise to the discussion of the model of the Snowball Earth. The emergence and evolution of skeletons in animals is sometimes thought to be connected with glaciations. These events are correlated and accounted for by great endogenous changes. One of the major events in endogenous history is the onset about 750 Ma of periodic manifestation of mantle flows (superplumes), which explain further periodicity of the biosphere evolution. In conclusion, extrapolation of future evolution and successive collapse of biosphere segments in the course of transformation of the Sun into a red star and warming of the Earth surface are proposed.     

When, where, and in what environment could the RNA world appear and evolve?

The environment necessary for the existence, amplification, and evolution of the RNA world, the difficulties of the abiogenous synthesis of RNA, and paradoxical situations with the stability of RNA, its functions, and the place of RNA in the geological history of the Earth are discussed. The chemical instability of the covalent structure of RNA in the aqueous medium is incompatible with the necessity of water for formation of its functionally active conformations (“water paradox”). The stable double-helical structure of RNA required for replication is incompatible with the stable compact conformations of single-stranded RNA molecules that are necessary for catalytic functions (conformational paradox). There was a very short time gap (or no gap at all) between the end of the massive meteorite bombardment of the Earth (3.9 Ga ago) and the appearance of the first evidence of cellular life (bacteria) in the Earth’s rocks (3.8–3.85 Ga ago or even earlier) (geological paradox). It is concluded that the RNA world could not appear, exist, or evolve into cellular forms of life on the Earth. This paper briefly discusses the possibility of an extraterrestrial origin of the RNA world and its extraterrestrial evolution with a subsequent distribution in space (mainly by comets) of the cellular form of life as more resistant to the environment as compared with free RNA.     

Geological constraints on the origin of oxygenic photosynthesis

This article examines the geological evidence for the rise of atmospheric oxygen and the origin of oxygenic photosynthesis. The evidence for the rise of atmospheric oxygen places a minimum time constraint before which oxygenic photosynthesis must have developed, and was subsequently established as the primary control on the atmospheric oxygen level. The geological evidence places the global rise of atmospheric oxygen, termed the Great Oxidation Event (GOE), between ~2.45 and ~2.32 Ga, and it is captured within the Duitschland Formation, which shows a transition from mass-independent to mass-dependent sulfur isotope fractionation. The rise of atmospheric oxygen during this interval is closely associated with a number of environmental changes, such as glaciations and intense continental weathering, and led to dramatic changes in the oxidation state of the ocean and the seawater inventory of transition elements. There are other features of the geologic record predating the GOE by as much as 200–300 million years, perhaps extending as far back as the Mesoarchean–Neoarchean boundary at 2.8 Ga, that suggest the presence of low level, transient or local, oxygenation. If verified, these features would not only imply an earlier origin for oxygenic photosynthesis, but also require a mechanism to decouple oxygen production from oxidation of Earth’s surface environments. Most hypotheses for the GOE suggest that oxygen production by oxygenic photosynthesis is a precondition for the rise of oxygen, but that a synchronous change in atmospheric oxygen level is not required by the onset of this oxygen source. The potential lag-time in the response of Earth surface environments is related to the way that oxygen sinks, such as reduced Fe and sulfur compounds, respond to oxygen production. Changes in oxygen level imply an imbalance in the sources and sinks for oxygen. Changes in the cycling of oxygen have occurred at various times before and after the GOE, and do not appear to require corresponding changes in the intensity of oxygenic photosynthesis. The available geological constraints for these changes do not, however, disallow a direct role for this metabolism. The geological evidence for early oxygen and hypotheses for the controls on oxygen level are the basis for the interpretation of photosynthetic oxygen production as examined in this review.     

Origins of life: A comparison of theories and application to Mars

The field of study that deals with the origins of life does not have a consensus for a theory of life's origin. An analysis of the range of theories offered shows that they share some common features that may be reliable predictors when considering the possible origins of life on another planet. The fundamental datum dealing with the origins of life is that life appeared early in the history of the Earth, probably before 3.5 Ga and possibly before 3.8 Ga. What might be called the standard theory (the Oparin-Haldane theory) posits the production of organic molecules on the early Earth followed by chemical reactions that produced increased organic complexity leading eventually to organic life capable of reproduction, mutation, and selection using organic material as nutrients. A distinct class of other theories (panspermia theories) suggests that life was carried to Earth from elsewhere — these theories receive some support from recent work on planetary impact processes. Other alternatives to the standard model suggest that life arose as an inorganic (clay) form and/or that the initial energy source was not organic material but chemical energy or sunlight. We find that the entire range of current theories suggests that liquid water is the quintessential environmental criterion for both the origin and sustenance of life. It is therefore of interest that during the time that life appeared on Earth we have evidence for liquid water present on the surface of Mars.     

Evolutionary timing of the origins of mesophilic sulphate reduction and oxygenic photosynthesis: a phylogenomic dating approach

Until recently, the deep‐branching relationships in the bacterial domain have been unresolved. A new phylogenetic approach (termed compartmentalization) was able to resolve these deep‐branching relationships successfully by using a large number of genes from whole genome sequences and by reducing long branch attraction artefacts. This new, well‐resolved phylogenetic tree reveals the evolutionary relationships between diverse bacterial groups that leave important traces in the geological record. It shows that mesophilic sulphate reducers originated before the Cyanobacteria, followed by the origination of sulphur‐ and pyrite‐oxidizing bacteria after oxygen became available in the biosphere. This evolutionary pattern mirrors a similar pattern in the Palaeoproterozoic geological record. Sulphur isotopic fractionation records indicate that large‐scale bacterial sulphate reduction began in marine environments around 2.45 billion years ago (Ga), followed by rapid oxygenation of the atmosphere about 2.3 or 2.2 Ga. Oxygenation was then followed by increasing oceanic sulphate concentrations (probably owing to pyrite oxidation and continental weathering), which then resulted in the disappearance of banded iron formations by 1.8 Ga. The similarity between the phylogenetic and geological records suggests that the geochemical changes observed on the Palaeoproterozoic Earth were caused by major origination events in the mesophilic bacteria, and that these geochemical changes then caused additional origination events, such as aerobic respiration. If so, then constraints on divergence dates can be established for many microbial groups, including the Cyanobacteria, mesophilic bacteria, mesophilic sulphate reducers, methanotrophs, several anoxygenic phototrophs, as well as for mitochondrial endosymbiosis. These dates may also help to explain a large number of other changes in the geological record of the Neoarchean and Palaeoproterozoic Earth. This hypothesis, however, does not agree with the finding of cyanobacterial and eukaryote lipids at 2.7 Ga, and suggests that further work needs to be done to elucidate the discrepancies in both these areas.     

Mars Primordial Crust: Unique Sites for Investigating Proto-biologic Properties

The Martian meteorite collection suggests that intact outcrops or boulder-scale fragments of the 4.5 Ga Martian crust exist within tens of meters of the present day surface of Mars. Mars may be the only planet where such primordial crust samples, representing the first 100 Ma of a planet’s environment, are available. The primordial crust has been destroyed on Earth by plate tectonics and other geological phenomena and is buried on the Moon under hundreds or thousands of meters of megaregoltih. Early Mars appears to have been remarkably similar to early Earth, and samples of rock from the first few Ma or first 100 Ma may reveal “missing link” proto-biological forms that could shed light on the transition from abiotic organic chemistry to living cells. Such organic snapshots of nascent life are unlikely to be found on Earth. Presented at: National Workshop on Astrobiology: Search for Life in the Solar System, Capri, Italy, 26 to 28 October, 2005.     

Atmospheric composition and climate on the early Earth

Oxygen isotope data from ancient sedimentary rocks appear to suggest that the early Earth was significantly warmer than today, with estimates of surface temperatures between 45 and 85 degrees C. We argue, following others, that this interpretation is incorrect-the same data can be explained via a change in isotopic composition of seawater with time. These changes in the isotopic composition could result from an increase in mean depth of the mid-ocean ridges caused by a decrease in geothermal heat flow with time. All this implies that the early Earth was warm, not hot.A more temperate early Earth is also easier to reconcile with the long-term glacial record. However, what triggered these early glaciations is still under debate. The Paleoproterozoic glaciations at approximately 2.4Ga were probably caused by the rise of atmospheric O2 and a concomitant decrease in greenhouse warming by CH4. Glaciation might have occurred in the Mid-Archaean as well, at approximately 2.9Ga, perhaps as a consequence of anti-greenhouse cooling by hydrocarbon haze. Both glaciations are linked to decreases in the magnitude of mass-independent sulphur isotope fractionation in ancient rocks. Studying both the oxygen and sulphur isotopic records has thus proved useful in probing the composition of the early atmosphere.     

Kinetic and Thermodynamic Analysis During Dissimilatory γ-FeOOH Reduction: Formation of Green Rust 1 and Magnetite

The oldest sedimentary rocks on Earth, the 3.8‐Ga Isua Iron‐Formation in southwestern Greenland, are metamorphosed past the point where organic‐walled fossils would remain. Acid residues and thin sections of these rocks reveal ferric microstructures that have filamentous, hollow rod, and spherical shapes not characteristic of crystalline minerals. Instead, they resemble ferric‐coated remains of bacteria. Modern so‐called iron bacteria were therefore studied to enhance a search image for oxide minerals precipitated by early bacteria. Iron bacteria become coated with ferrihydrite, a metastable mineral that converts to hematite, which is stable under high temperatures. If these unusual morphotypes are mineral remains of microfossils, then life must have evolved somewhat earlier than 3.8 Ga, and may have involved the interaction of sediments and molecular oxygen in water, with iron as a catalyst. Timing is constrained by the early in fall of planetary materials that would have heated the planet's surface.

Because there are no earlier sedimentary rocks to study on Earth, it may be necessary to expand the search elsewhere in the solar system for clues to any biotic precursors or other types of early life. Evidence from Mars shows geophysical and geochemical differentiation at a very early stage, which makes it an important candidate for such a search if sedimentation is an important process in life's origins. Not only does Mars have iron oxide‐rich soils, but its oldest regions have river channels where surface water and sediment may have been carried, and seepage areas where groundwater may have discharged. Mars may have had an atmosphere and liquid water in the crucial time frame of 3.9–4.0 Ga. A study of morphologies of iron oxide minerals collected in the southern highlands during a Mars sample return mission may therefore help to fill in important gaps in the history of Earth's earliest biosphere.     

The oxygenation of the atmosphere and oceans

The last 3.85 Gyr of Earth history have been divided into five stages. During stage 1 (3.85-2.45 Gyr ago (Ga)) the atmosphere was largely or entirely anoxic, as were the oceans, with the possible exception of oxygen oases in the shallow oceans. During stage 2 (2.45-1.85 Ga) atmospheric oxygen levels rose to values estimated to have been between 0.02 and 0.04 atm. The shallow oceans became mildly oxygenated, while the deep oceans continued anoxic. Stage 3 (1.85-0.85 Ga) was apparently rather 'boring'. Atmospheric oxygen levels did not change significantly. Most of the surface oceans were mildly oxygenated, as were the deep oceans. Stage 4 (0.85-0.54 Ga) saw a rise in atmospheric oxygen to values not much less than 0.2 atm. The shallow oceans followed suit, but the deep oceans were anoxic, at least during the intense Neoproterozoic ice ages. Atmospheric oxygen levels during stage 5 (0.54 Ga-present) probably rose to a maximum value of ca 0.3 atm during the Carboniferous before returning to its present value. The shallow oceans were oxygenated, while the oxygenation of the deep oceans fluctuated considerably, perhaps on rather geologically short time-scales.     

Microbes: Mini Iron Factories

Microbes have flourished in extreme habitats since beginning of the Earth and have played an important role in geological processes like weathering, mineralization, diagenesis, mineral formation and destruction. Biotic mineralization is one of the most fascinating examples of how microbes have been influencing geological processes. Iron oxidizing and reducing bacteria are capable of precipitating wide varieties of iron oxides (magnetite), carbonates (siderite) and sulphides (greigite) via controlled or induced mineralization processes. Microbes have also been considered to play an important role in the history of evolution of sedimentary rocks on Earth from the formation of banded iron formations during the Archean to modern biotic bog iron and ochre deposits. Here, we discuss the role that microbes have been playing in precipitation of iron and the role and importance of interdisciplinary studies in the field of geology and biology in solving some of the major geological mysteries.     

Adaptive signals in algal Rubisco reveal a history of ancient atmospheric carbon dioxide

Rubisco, the most abundant enzyme on the Earth and responsible for all photosynthetic carbon fixation, is often thought of as a highly conserved and sluggish enzyme. Yet, different algal Rubiscos demonstrate a range of kinetic properties hinting at a history of evolution and adaptation. Here, we show that algal Rubisco has indeed evolved adaptively during ancient and distinct geological periods. Using DNA sequences of extant marine algae of the red and Chromista lineage, we define positive selection within the large subunit of Rubisco, encoded by rbcL, to occur basal to the radiation of modern marine groups. This signal of positive selection appears to be responding to changing intracellular concentrations of carbon dioxide (CO(2)) triggered by physiological adaptations to declining atmospheric CO(2). Within the ecologically important Haptophyta (including coccolithophores) and Bacillariophyta (diatoms), positive selection occurred consistently during periods of falling Phanerozoic CO(2) and suggests emergence of carbon-concentrating mechanisms. During the Proterozoic, a strong signal of positive selection after secondary endosymbiosis occurs at the origin of the Chromista lineage (approx. 1.1 Ga), with further positive selection events until 0.41 Ga, implying a significant and continuous decrease in atmospheric CO(2) encompassing the Cryogenian Snowball Earth events. We surmise that positive selection in Rubisco has been caused by declines in atmospheric CO(2) and hence acts as a proxy for ancient atmospheric CO(2).     

Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus

A rearranged murine V kappa 8/J kappa 5 L chain gene that codes for the L chain of most antibodies generated in the primary response of BALB/c mice to the antigenic site, Sb, of the hemagglutinin (HA) molecule of influenza virus A/PR/8/34 (PR8) has been cloned. Three transgenic lines were generated by microinjecting the gene. Lines Ga and L each contain a single copy of the transgene whereas line Gb contains three complete copies. Mice of the Ga lineage showed increased V kappa 8-specific mRNA levels only in spleen, but not in nonlymphoid organs and therefore displayed apparently normal lymphoid-specific regulation of the Ig transgene. B cell hybridomas generated from these mice were analyzed for rearrangements of endogenous V kappa genes. Greater than 90% of the C kappa alleles were retained in germ-line configuration in the Ga line, compared with only 0 to 18% in the L line. Thus, a wide variation in the frequency of endogenous rearrangements is seen among mice of different lineages using the same transgene construct. None of more than 150 hybridomas derived from LPS-stimulated splenic B cells of Ga mice exhibited HA-binding activity although they expressed the transgene and, in most cases, excluded endogenous V kappa rearrangements. In contrast, a large fraction of hybridomas isolated after primary immunization with PR8 were HA(Sb)-specific. This indicated that the transgene was functional but formed HA-specific antibodies with a more restricted set of H chains than previously hypothesized. The primary anti-HA response to immunization with PR8 was diminished in all lines compared with normal mice except for a slightly accelerated but transient burst of anti-HA antibody formation in two out of three lines (Ga and Gb). This early response in G lineage mice was largely specific for HA(Sb) and thus appeared to be composed of transgene-expressing antibodies. No differences in serum titers were observed in the secondary anti-HA responses to booster inoculation with PR8 between transgenic and normal mice.     

Humic substances in the early biosphere

Humic substances and their organic-mineral compounds are the first stage in transformation of biotic residues into stable geopolymers, which comprise the main reservoir of organic C in the biosphere. Early appearance of HS in the Earth’s history is of principal importance for the understanding of geo-biological processes on land in the past. However, there is no fossil record of HS before land colonization by lignified vegetation (400 Ma). When the first soil HS were formed? Could HS be synthesized in the Precambrian before plants and mosses terrestrialization? The formation of HS occurs in mesophilic aerobic conditions and requires presence of oxidative catalysts and production of aromatic (phenolic) precursors by biota. In this paper, humification processes in algo-myco-bacterial and lichen communities are discussed from actualistic point of view. These communities are considered as a relict ecosystem, which could dominate on land during the Neoproterozoic-Early Paleozoic (1–0.5 Ga).     

Crown group Oxyphotobacteria postdate the rise of oxygen

The rise of oxygen ca. 2.3 billion years ago (Ga) is the most distinct environmental transition in Earth history. This event was enabled by the evolution of oxygenic photosynthesis in the ancestors of Cyanobacteria. However, long‐standing questions concern the evolutionary timing of this metabolism, with conflicting answers spanning more than one billion years. Recently, knowledge of the Cyanobacteria phylum has expanded with the discovery of non‐photosynthetic members, including a closely related sister group termed Melainabacteria, with the known oxygenic phototrophs restricted to a clade recently designated Oxyphotobacteria. By integrating genomic data from the Melainabacteria, cross‐calibrated Bayesian relaxed molecular clock analyses show that crown group Oxyphotobacteria evolved ca. 2.0 billion years ago (Ga), well after the rise of atmospheric dioxygen. We further estimate the divergence between Oxyphotobacteria and Melainabacteria ca. 2.5–2.6 Ga, which—if oxygenic photosynthesis is an evolutionary synapomorphy of the Oxyphotobacteria—marks an upper limit for the origin of oxygenic photosynthesis. Together, these results are consistent with the hypothesis that oxygenic photosynthesis evolved relatively close in time to the rise of oxygen.     

Evolution of geological processes on the early earth and their impact on the early biosphere

Although life already existed in the Paleoarchean (ca. 3.8 Ga), rapid development of the biosphere began only in the Paleoproterozoic, from 2.4–2.3 Ga; this eventually resulted in the emergence of multicellular organisms. This event coincided in time with the irreversible replacement of tectonomagmatic activity, when high-Mg magmatism of the Early Precambrian, derived from depleted mantle, was irreversibly replaced by geochemically enriched Fe-Ti basalts similar to Phanerozoic intraplate magmas. The new type of magmas was characterized by the increased and high content of Fe, Ti, Cu, P, Mn, alkalis, LREE, and other incompatible elements (Zr, Ba, Sr, U, Th, F, etc.), which are required for metabolism and fermentation. It is proposed that this event promoted changes in ecological conditions and rapid development of the biosphere, providing the Earth’s surface with qualitatively new biotic material.     

The geological setting of the earliest life forms

Summary Life on Earth may have begun about 4×10⁹ years (4 Ga) ago. Plate tectonics probably operated in the early Archaean, with rapid spreading at mid-ocean ridges, a komatiitic (magnesium-rich) oceanic crust, active volcanic arcs and the development of extensional basins on continental crust. Shallow water environments would have been more restricted and probably shorter-lived than in later geological times; however, extensive shallow seas existed in the later phases of the development of extensional basins. Bacterial communities-presumably photosynthetic-have probably existed in such shallow-water settings and probably at shallow depths in the oceans for at least 3.5 Ga. Because the mid-ocean ridges were probably subaqueous, hydrothermal systems would have been very vigorous and would have offered suitable habitats for early chemo-autotrophic bacterial communities. Early life forms probably also occupied vesicles in lavas, pumice and volcanic breccias, and pores in soft sediments, living in the constant flux of fluid flushing through permeable strata. Other, similar habitats would have existed in volcanic island arcs and in extensional basins.     

Interaction,at Ambient Temperature and 80 °C,between Minerals and Artificial Seawaters Resembling the Present Ocean Composition and that of 4.0 Billion Years Ago

Probably one of the most important roles played by minerals in the origin of life on Earth was to pre-concentrate biomolecules from the prebiotic seas. There are other ways to pre concentrate biomolecules such as wetting/drying cycles and freezing/sublimation. However, adsorption is most important. If the pre-concentration did not occur—because of degradation of the minerals—other roles played by them such as protection against degradation, formation of polymers, or even as primitive cell walls would be seriously compromised. We studied the interaction of two artificial seawaters with kaolinite, bentonite, montmorillonite, goethite, ferrihydrite and quartz. One seawater has a major cation and anion composition similar to that of the oceans of the Earth 4.0 billion years ago (ASW 4.0 Ga). In the other, the major cations and anions are an average of the compositions of the seawaters of today (ASWT). When ASWT, which is rich in Na⁺ and Cl^?, interacted with bentonite and montmorrilonite structural collapse occurred on the 001 plane. However, ASW 4.0 Ga, which is rich in Mg²⁺ and SO₄ ^2?, did not induce this behavior. When ASW 4.0 Ga was reacted with the minerals for 24 h at room temperature and 80 °C, the release of Si and Al to the fluid was below 1 % of the amount in the minerals—meaning that dissolution of the minerals did not occur. In general, minerals adsorbed Mg²⁺ and K⁺ from the ASW 4.0 Ga and these cations could be used for the formation of polymers. Also, when the minerals were mixed with ASW 4.0 Ga at 80 °C and ASWT at room temperature or 80 °C it caused the precipitation of CaSO₄?2H₂O and halite, respectively. Finally, further experiments (adsorption, formation of polymers, protection of molecules against degradation, primitive cell wall formation) performed under the conditions described in this paper will probably be more representative of what happened on the prebiotic Earth.     

Cataclysm No More: New Views on the Timing and Delivery of Lunar Impactors

If properly interpreted, the impact record of the Moon, Earth’s nearest neighbour, can be used to gain insights into how the Earth has been influenced by impacting events since its formation ~4.5 billion years (Ga) ago. However, the nature and timing of the lunar impactors – and indeed the lunar impact record itself – are not well understood. Of particular interest are the ages of lunar impact basins and what they tell us about the proposed “lunar cataclysm” and/or the late heavy bombardment (LHB), and how this impact episode may have affected early life on Earth or other planets. Investigations of the lunar impactor population over time have been undertaken and include analyses of orbital data and images; lunar, terrestrial, and other planetary sample data; and dynamical modelling. Here, the existing information regarding the nature of the lunar impact record is reviewed and new interpretations are presented. Importantly, it is demonstrated that most evidence supports a prolonged lunar (and thus, terrestrial) bombardment from ~4.2 to 3.4 Ga and not a cataclysmic spike at ~3.9 Ga. Implications for the conditions required for the origin of life are addressed.     

The concept of macroevolution in view of modern data

Macroevolution, or evolution of superspecies taxa is the process of transformation of “organismal” life flows on the Earth during its geological history. In the present study, this process is analyzed with using the system and evolutionarily?ecological approaches. Based on modern paleontological, evolutionary biological, molecular, and genetic data, mostly on vertebrates and hominins, the major factors and patterns of macroevolution and also the role of macroevolution in the biosphere evolution are discussed. The fundamental bases of the concept of macroevolution, the problems of methodology and methods of the study of organismal evolution are considered. It is shown that the processes at the macroevolutionary level agree with the epigenetic theory of evolution.     

Solution structure of the dimeric cytoplasmic domain of syndecan-4.

The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4 cytoplasmic domain is dependent on its oligomeric status, the conformation of the syndecan-4 cytoplasmic domain itself is important in the understanding of its biological roles. Gel filtration results show that the syndecan-4 cytoplasmic domain (4L) itself forms a dimer stabilized by ionic interactions between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195). The molecular surface of the 4L dimer is highly positively charged. In addition, no intersubunit NOEs in membrane proximal amino acid resides (C1 region) have been observed, demonstrating that the C1 region is mostly unstructured in the syndecan-4L dimer. Interestingly, two parallel strands of 4L form a cavity in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected by the presence of C1 and C2 regions. Therefore, we propose that although the 4V region in the full cytoplasmic domain has a tendency for strong peptide--peptide interaction, it may not be enough to overcome the repulsion of the C1 regions of syndecan-4L.