Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast

In the postgenomic era, one of the most interesting and important challenges is to understand protein interactions on a large scale. The physical interactions between protein domains are fundamental to the workings of a cell: in multi-domain polypeptide chains, in multi-subunit proteins and in transient complexes between proteins that also exist independently. To study the large-scale patterns and evolution of interactions between protein domains, we view interactions between protein domains in terms of the interactions between structural families of evolutionarily related domains. This allows us to classify 8151 interactions between individual domains in the Protein Data Bank and the yeast Saccharomyces cerevisiae in terms of 664 types of interactions, between protein families. At least 51 interactions do not occur in the Protein Data Bank and can only be derived from the yeast data. The map of interactions between protein families has the form of a scale-free network, meaning that most protein families only interact with one or two other families, while a few families are extremely versatile in their interactions and are connected to many families. We observe that almost half of all known families engage in interactions with domains from their own family. We also see that the repertoires of interactions of domains within and between polypeptide chains overlap mostly for two specific types of protein families: enzymes and same-family interactions. This suggests that different types of protein interaction repertoires exist for structural, functional and regulatory reasons. Copyright 12001 Academic Press.     

Greeting behavior during party encounters in captive chimpanzees

Party encounter situations were experimentally produced in a group of captive chimpanzees (Pan troglodytes verus) at the Primate Research Institute of Kyoto University, Japan. During weekends all subjects (two adult males and five adult females) usually stayed together in the rooms (Baseline condition). Under experimental conditions, we shut passages between rooms to divide the subjects into two groups. We examined the effects of temporal separation of group members on affiliative interactions, aggressive interactions, and simple proximity. The frequency of affiliative interactions between male and female chimpanzees and between female chimpanzees increased when they encountered one another after separation, irrespective of male identity or housing history. Therefore we considered affiliative interactions between males and females during party encounters as being the response between separated individuals. The same tendency was not found in the frequency of affiliative interactions between females or between males. Unlike affiliative interactions, neither aggressive interactions nor simple proximity were influenced by separation.     

Principles of protein-protein interactions

In the postgenomic era, one of the most interesting and important challenges is to understand protein interactions on a large scale. The physical interactions between protein domains are fundamental to the workings of a cell: in multi-domain polypeptide chains, in multi-subunit proteins and in transient complexes between proteins that also exist independently. Thus experimental investigation of protein-protein interactions has been extensive, including recent large-scale screens using mass spectrometry. The role of computational research on protein-protein interactions encompasses not only prediction, but also understanding the nature of the interactions and their three-dimensional structures. I will discuss properties such as sequence conservation and co-regulation of genes and proteins involved in different types of physical interactions. Given that all proteins consist of their evolutionary units, the domains, all interactions occur between these domains. The interactions between domains belonging to different protein families will be the second topic of my talk.     

An assessment of biological interactions in an epilithic stream community using time-lapse cinematography

In situ time-lapse cinematography was used to record and enumerate behavioral interactions between members of an epilithic insect community in a small Michigan (U.S.A.)trout stream. 145 interactions were observed during 78 hours of filming. Most of these (98%) involved simuliid larvae. Interactions between simuliid larvae occurred at about the same frequency as interactions between simuliids and other taxa. However, interactions between simuliid larvae were less likely to lead to emigration than were interactions between blackflies and other groups. Significant short-term fluctuations of faunal density on filmed surfaces were also observed. The causes of these fluctuations appeared varied. The results of a preliminary assessment of interactions and the usefulness of this technique are discussed.     

Molecular simulation of the effect of cholesterol on lipid-mediated protein-protein interactions

Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid-mediated protein-protein interactions. In this article, we discuss the effect of cholesterol on lipid-mediated protein-protein interactions as function of hydrophobic mismatch, protein diameter and protein cluster size, lipid tail length, and temperature. To do so, we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded, with a hybrid dissipative particle dynamics-Monte Carlo method. We propose a mechanism by which cholesterol affects protein interactions: protein-induced, cholesterol-enriched, or cholesterol-depleted lipid shells surrounding the proteins affect the lipid-mediated protein-protein interactions. Our calculations of the potential of mean force between proteins and protein clusters show that the addition of cholesterol dramatically reduces repulsive lipid-mediated interactions between proteins (protein clusters) with positive mismatch, but does not affect attractive interactions between proteins with negative mismatch. Cholesterol has only a modest effect on the repulsive interactions between proteins with different mismatch.     

Influence of predator density on nonindependent effects of multiple predator species

Interactions between multiple predator species are frequent in natural communities and can have important implications for shared prey survival. Predator density may be an important component of these interactions between predator species, as the frequency of interactions between species is largely determined by species density. Here we experimentally examine the importance of predator density for interactions between predator species and subsequent impacts on prey. We show that aggressive interactions between the predatory shore crabs Carcinus maenas and Hemigrapsus sanguineus increased with predator density, yet did not increase as fast as negative interactions between conspecifics. At low density, interactions between conspecific and heterospecific predators had similar inhibitory impacts on predator function, whereas conspecific interference was greater than interference from heterospecifics at high predator density. Thus the impact of conspecific interference at high predator density was sufficient in itself that interactions with a second predator species had no additional impact on per capita predation. Spatial and temporal variability in predator density is a ubiquitous characteristic of natural systems that should be considered in studies of multiple predator species.     

Sidechain interactions in parallel beta sheets: the energetics of cross-strand pairings

BACKGROUND: Both backbone hydrogen bonding and interactions between sidechains stabilize beta sheets. Cross-strand interactions are the closest contacts between the sidechains of a beta sheet. Here we investigate the energetics of cross-strand interactions using a variant of the B1 domain of immunoglobulin G (IgG) binding protein G (beta1) as our model system. RESULTS: Pairwise mutations of polar and nonpolar residues were made at a solvent-exposed site between the two central parallel beta strands of beta1. Both stabilizing and destabilizing interactions were measured. The greatest stabilizations were observed for charge-charge interactions. Our experimental study of sidechain interactions correlates with statistical preferences: residue pairs for which we measure stabilizing interaction energies occur together frequently, whereas destabilizing pairs are rarely observed together. CONCLUSIONS: Sidechain interactions modulate the stability of beta sheets. We propose that cross-strand sidechain interactions specify correct strand register and ordering through the energetic benefit of optimally arranged pairings.     

Transient protein-protein interactions: structural, functional, and network properties

Transient interactions, which involve protein interactions that are formed and broken easily, are important in many aspects of cellular function. Here we describe structural and functional properties of transient interactions between globular domains and between globular domains, short peptides, and disordered regions. The importance of posttranslational modifications in transient interactions is also considered. We review techniques used in the detection of the different types of transient protein-protein interactions. We also look at the role of transient interactions within protein-protein interaction networks and consider their contribution to different aspects of these networks.     

A Bead Aggregation Assay for Detection of Low-Affinity Protein-Protein Interactions Reveals Interactions between N-Terminal Domains of Inositol 1,4,5-Trisphosphate Receptors

Interactions between proteins are a hallmark of all cellular activities. Such interactions often occur with low affinity, a feature that allows them to be rapidly reversible, but it makes them difficult to detect using conventional methods such as yeast 2-hybrid analyses, co-immunoprecipitation or analytical ultracentrifugation. We developed a simple and economical bead aggregation assay to study low-affinity interactions between proteins. By coating beads with interacting proteins, the weak interactions between many proteins are sufficient to allow stable aggregation of beads, an avidity effect. The aggregation is easily measured to allow quantification of protein-protein interactions under a variety of controlled conditions. We use this assay to demonstrate low-affinity interactions between the N-terminal domains of an intracellular Ca²⁺ channel, the type 1 inositol 1,4,5-trisphosphate receptor. This simple bead aggregation assay may have widespread application in the study of low-affinity interactions between macromolecules.     

Yeast two hybrid analyses reveal novel binary interactions between human cytomegalovirus-encoded virion proteins

Human cytomegalovirus (HCMV) is the largest human herpesvirus and its virion contains many viral encoded proteins found in the capsid, tegument, and envelope. In this study, we carried out a yeast two-hybrid (YTH) analysis to study potential binary interactions among 56 HCMV-encoded virion proteins. We have tested more than 3,500 pairwise combinations for binary interactions in the YTH analysis, and identified 79 potential interactions that involve 37 proteins. Forty five of the 79 interactions were also identified in human cells expressing the viral proteins by co-immunoprecipitation (co-IP) experiments. To our knowledge, 58 of the 79 interactions revealed by YTH analysis, including those 24 that were also identified in co-IP experiments, have not been reported before. Novel potential interactions were found between viral capsid proteins and tegument proteins, between tegument proteins, between tegument proteins and envelope proteins, and between envelope proteins. Furthermore, both the YTH and co-IP experiments have identified 9, 7, and 5 interactions that were involved with UL25, UL24, and UL89, respectively, suggesting that these "hub" proteins may function as the organizing centers for connecting multiple virion proteins in the mature virion and for recruiting other virion proteins during virion maturation and assembly. Our study provides a framework to study potential interactions between HCMV proteins and investigate the roles of protein-protein interactions in HCMV virion formation or maturation process.     

Who's In and Who's Out—Compositional Control of Biomolecular Condensates

Biomolecular condensates are two- and three-dimensional compartments in eukaryotic cells that concentrate specific collections of molecules without an encapsulating membrane. Many condensates behave as dynamic liquids and appear to form through liquid–liquid phase separation driven by weak, multivalent interactions between macromolecules. In this review, we discuss current models and data regarding the control of condensate composition, and we describe our current understanding of the composition of representative condensates including PML nuclear bodies, P-bodies, stress granules, the nucleolus, and two-dimensional membrane localized LAT and nephrin clusters. Specific interactions, such as interactions between modular binding domains, weaker interactions between intrinsically disorder regions and nucleic acid base pairing, and nonspecific interactions, such as electrostatic interactions and hydrophobic interactions, influence condensate composition. Understanding how specific condensate composition is determined is essential to understanding condensates as biochemical entities and ultimately discerning their cellular and organismic functions.     

Homotypic fibrillin-1 interactions in microfibril assembly

We have defined the homotypic interactions of fibrillin-1 to obtain new insights into microfibril assembly. Dose-dependent saturable high affinity binding was demonstrated between N-terminal fragments, between furin processed C-terminal fragments, and between these N- and C-terminal fragments. The N terminus also interacted with a downstream fragment. A post-furin cleavage site C-terminal sequence also interacted with the N terminus, with itself and with the furin-processed fragment. No other homotypic fibrillin-1 interactions were detected. Some terminal homotypic interactions were inhibited by other terminal sequences, and were strongly calcium-dependent. Treatment of an N-terminal fragment with N-ethylmaleimide reduced homotypic binding. Microfibril-associated glycoprotein-1 inhibited N- to C-terminal interactions but not homotypic N-terminal interactions. These fibrillin-1 interactions are likely to regulate pericellular fibrillin-1 microfibril assembly.     

Lectins and recognition of protein ligands

The general principles of protein-carbohydrate lectin interactions were discussed. Experimental evidences of the molecular mimicry between carbohydrate and protein lectin ligands were analyzed. The interdomain interactions in lectins as well as the interactions between ligands and lectin domains other than carbohydrate-binding domains were considered.     

白假丝酵母与细菌相互作用机制及其与感染的关系

人体内定植着数目庞大、结构复杂的细菌及真菌等微生物群,它们之间存在复杂的相互作用。既往研究主要集中于细菌或真菌的某个单一物种,但最近研究表明,细菌与真菌之间的相互作用对更好地理解体内的微生态系统至关重要。白假丝酵母(又称白念珠菌)是人备体中最常见的机会性致病真菌,通常被认为是人类正常菌群的一部分。白念珠菌与细菌的相互作用近年来备受关注,其协同和拮抗作用有助于维持不同物种间复杂的平衡关系。了解白念珠菌与细菌的相互作用,不仅可加深对微生物致病机制的理解,还可为预防和治疗白念珠菌或细菌感染及新型抗菌药物研发提供新途径。本文就白念珠菌与细菌共存时的相互作用机制及其对人类健康、疾病的影响进行综述,从而为控制念珠菌或细菌感染提供新的策略。     

Structural basis of specific TraD-TraM recognition during F plasmid-mediated bacterial conjugation

F plasmid-mediated bacterial conjugation requires interactions between a relaxosome component, TraM, and the coupling protein TraD, a hexameric ring ATPase that forms the cytoplasmic face of the conjugative pore. Here we present the crystal structure of the C-terminal tail of TraD bound to the TraM tetramerization domain, the first structural evidence of relaxosome-coupling protein interactions. The structure reveals the TraD C-terminal peptide bound to each of four symmetry-related grooves on the surface of the TraM tetramer. Extensive protein-protein interactions were observed between the two proteins. Mutational analysis indicates that these interactions are specific and required for efficient F conjugation in vivo. Our results suggest that specific interactions between the C-terminal tail of TraD and the TraM tetramerization domain might lead to more generalized interactions that stabilize the relaxosome-coupling protein complex in preparation for conjugative DNA transfer.     

Interactions between germ cells and somatic cells in Drosophila melanogaster

Interactions between germ cells and somatic cells are important at several stages of Drosophila development. The types of interactions that will be discussed include: (1) molecules physically transferred from one cell to another; (2) long range interactions by hormones; and (3) local interactions between germ cells and somatic cells when they are in close proximity. These interactions have been mostly characterized during oogenesis.     

Epistat : a computer program for identifying and testing interactions between pairs of quantitative trait loci

 We describe a computer program, Epistat, which combines statistical methods and color-graphic displays to facilitate the analysis of interactions between pairs of quantitative trait loci (QTLs). Epistat organizes genetic-mapping data and quantitative-trait values into graphic displays which illustrate the individual effects of single loci as well as the interactions between any two loci. Keyboard commands allow the user to search the data set for individual QTLs and to test for interactions between QTLs. For a given trait, the program displays the effects of the alleles at each of two loci on the quantitative-trait value, as well as the effects of the interactions between these alleles. Loglikelihood ratios are used to compare the likelihood of explaining the effects by null, additive, or epistatic models. Examples of interactions in soybean are presented for near-infrared transmittance (NIT), seed number, and reproductive period. Epistat has been used to find numerous interactions between QTLs in soybean in which trait variation at one locus is conditional upon a specific allele at another. Received: 16 January 1996 / Accepted: 27 September 1996     

Neutral currents in weak interactions and molecular asymmetry

Weak interactions are parity violating forces, i.e. they differentiate between mirror images. Therefore it is a very attractive hypothesis to invoke weak interactions in explaining the origin of molecular asymmetry. It is, however, not clear whether weak interactions may operate between electrons and/or between electrons and protons? For these types of interactions so called neutral currents are needed. Recent experiments with muon neutrinos at CERN gave some evidence for the existence of neutral currents. Thus we may suppose that parity violating forces are active in molecules. In the first part of this paper a very elementary theory of weak interactions is outlined with special reference to the discovery of neutral currents. In the second part we show how weak interactions may differentiate between mirror image molecules. The asymmetrically distributed static charges in chiral molecules represent a helical potential field. This potential field may exert an effect on the orbital electrons and therefore coupling of spins and momenta occurs. Thus the enantiomers are parity transformed images not only as geometrical bodies, but their orbital electrons are parity transformed too as "a helical electron gas". Weak interactions will differentiate between L and D forms because their orbital electrons have a nonzero spin polarization with respect to their velocity.