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1.
Mitochondria make physical contact with nearly every other membrane in the cell, and these contacts have a wide variety of functions that are carried out by proteins that reside at the sites of contact. Over the past decade, tremendous insight into the identity and functions of proteins localized to mitochondrial contact sites has been gained. In doing so, it has become clear that one protein or protein complex can contribute to contact site formation and function in a wide variety of ways. Thus, complex and often surprising relationships between the roles of a mitochondrial contact site and its multifunctional resident proteins continue to be unraveled. 相似文献
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Summary Several E. coli mutants were isolated which produce triple chimeras between one of the trp enzymes lac, repressor and -galactosidase. The mutants were isolated as TonB- Lac+ derivatives of a phenotypically Lac- TrpR- strain carrying a lac I
+-Z+ fusion on a 80dlac phage. The phage is integrated into the chromosome in such a way that the lac and the trp genes are transcribed in the same direction. Of a total of 58 candidates 2 TrpA- and 3 Trp- strains produce triple chimeras. The chimeras from the two TrpA- strains were further examined. They consist of tryptophan synthetase -subunit, lac repressor and -galactosidase. In crude extracts of these strains the tryptophan synthetase -subunit part can be identified by its ability to aggregate with the -subunit since some of the -subunit activity can be precipitated with antiserum against -galactosidase. Furthermore -galactosidase precipitates with antiserum against tryptophan synthetase -subunit. The lac repressor part is able to bind IPTG, but not lac operator DNA in vitro. The -galactosidase part is as unaffected as in the original lac repressor--galactosidase chimera. The molecular weigths of both chimeras are 175,000 when determined by SDS gel electrophoresis. The chimeras are partially degraded giving rise to fragments of distinct molecular weights. 相似文献
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Willars GB 《Seminars in cell & developmental biology》2006,17(3):363-376
Regulators of G-protein signalling (RGS) proteins are a large and diverse family initially identified as GTPase activating proteins (GAPs) of heterotrimeric G-protein Galpha-subunits. At least some can also influence Galpha activity through either effector antagonism or by acting as guanine nucleotide dissociation inhibitors (GDIs). As our understanding of RGS protein structure and function has developed, so has the realisation that they play roles beyond G-protein regulation. Such diversity of function is enabled by the variety of RGS protein structure and their ability to interact with other cellular molecules including phospholipids, receptors, effectors and scaffolds. The activity, sub-cellular distribution and expression levels of RGS proteins are dynamically regulated, providing a layer of complexity that has yet to be fully elucidated. 相似文献
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The classic structure–function paradigm holds that a protein exhibits a single well-defined native state that gives rise to its biological function. Nonetheless, over the past few decades, numerous examples of proteins exhibiting biological function arising from multiple structural states of varying disorder have been identified. Most recently, several examples of ‘metamorphic proteins’, able to interconvert between vastly different native-like topologies under physiological conditions, have been characterised with multiple functions. In this review, we look at the concept of protein metamorphosis in relation to the current understanding of the protein structure–function landscape. Although structural dynamism observed for metamorphic proteins provides a novel source of functional versatility, the dynamic nature of the metamorphic proteins generally makes them difficult to identify and probe using conventional protein structure determination methods. However, as the existence of metamorphic proteins has now been established and techniques enabling the analysis of multiple protein conformers are improving, it is likely that this class will continue to grow in number. 相似文献
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《Cell calcium》2018
Calcium (Ca2+) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca2+ homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca2+ within cells and a number of physiological agonists mediate ER Ca2+ release by activating IP3 receptors (IP3R). This decrease in ER Ca2+ levels is sensed by STIM, which physically interacts and activates plasma membrane Ca2+ selective Orai channels. Emerging literature implicates a key role for STIM1, STIM2, Orai1 and Orai3 in regulating both cell survival and death pathways. In this review, we will retrospect the work highlighting the role of STIM and Orai homologs in regulating cell death signaling. We will further discuss the rationales that could explain the dual role of STIM and Orai proteins in regulating cell fate decisions. 相似文献
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Checler F 《IUBMB life》1999,48(1):33-39
Early-onset aggressive forms of Alzheimer's disease (AD) are of genetic nature and have been linked to inherited mutations located on chromosomes 21, 14, and 1. The gene products of chromosomes 14 and 1, which are responsible for most of these familial forms of the disease (FAD), have been recently identified and referred to as presenilin 1 and 2 (PS1, PS2), respectively. Several lines of evidence derived from neuropathological, cell biology, and transgenesis approaches indicate that PS could interfere with the processing of the beta-amyloid precursor protein (betaAPP). Thus, FAD-linked mutations in PS exacerbate the production of Abeta42, the readily aggregable Abeta species corresponding to one of the main constituents of the senile plaques that invade the cortical areas of affected brains. Recent studies indicate that PS functions could be intimately related with the susceptibility of PS to further processing by caspase-like enzymes and other unknown proteolytic activities. Here I briefly report on the post-translational events undergone by PS and examine recent advances concerning their possible roles in development, cell signaling, and apoptosis. Possible alterations brought by FAD-linked mutations will be discussed. 相似文献
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Ubiquitin and ubiquitin-like proteins as multifunctional signals 总被引:1,自引:0,他引:1
Protein ubiquitylation is a recognized signal for protein degradation. However, it is increasingly realized that ubiquitin conjugation to proteins can be used for many other purposes. Furthermore, there are many ubiquitin-like proteins that control the activities of proteins. The central structural element of these post-translational modifications is the ubiquitin superfold. A common ancestor based on this superfold has evolved to give various proteins that are involved in diverse activities in the cell. 相似文献
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Giuliano Bellapadrona Matteo Ardini Pierpaolo Ceci Simonetta Stefanini Emilia Chiancone 《Free radical biology & medicine》2010,48(2):292-297
Dps (DNA-binding proteins from starved cells) proteins belong to a widespread bacterial family of proteins expressed under nutritional and oxidative stress conditions. In particular, Dps proteins protect DNA against Fenton-mediated oxidative stress, as they catalyze iron oxidation by hydrogen peroxide at highly conserved ferroxidase centers and thus reduce significantly hydroxyl radical production. This work investigates the possible generation of intraprotein radicals during the ferroxidation reaction by Escherichia coli and Listeria innocua Dps, two representative members of the family. Stopped-flow analyses show that the conserved tryptophan and tyrosine residues located near the metal binding/oxidation center are in a radical form after iron oxidation by hydrogen peroxide. DNA protection assays indicate that the presence of both residues is necessary to limit release of hydroxyl radicals in solution and the consequent oxidative damage to DNA. In general terms, the demonstration that conserved protein residues act as a trap that dissipates free electrons generated during the oxidative process brings out a novel role for the Dps protein cage. 相似文献
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Havukainen H Haataja S Kauko A Pulliainen AT Salminen A Haikarainen T Finne J Papageorgiou AC 《Protein science : a publication of the Protein Society》2008,17(9):1513-1521
Streptococcus suis Dpr is an iron-binding protein involved in oxidative stress resistance. It belongs to the bacterial Dps protein family whose members form dodecameric assemblies. Previous studies have shown that zinc and terbium inhibit iron incorporation in Listeria innocua Dps protein. In order to gain structural insights into the inhibitory effect of zinc and terbium, the crystal structures of Streptococcus suis Dpr complexes with these ions were determined at 1.8 A and 2.1 A, respectively. Both ions were found to bind at the ferroxidase center and in the same location as iron. In addition, a novel zinc-binding site formed by His40 and His44 was identified. Both His residues were found to be present within all known Streptococcus suis Dpr variants and in Streptococcus pneumoniae, Streptococcus gordonii, and Streptococcus sanguinis Dpr proteins. Amino acid sequence alignment of Dpr with other Dps family members revealed that His44 is highly conserved, in contrast to His40. The inhibitory effect of zinc and terbium on iron oxidation in Dpr was studied in vitro, and it was found that both ions at concentrations >0.2 mM almost completely abolish iron binding. These results provide a structural basis for the inhibitory effect of zinc and terbium in the Dps family of proteins, and suggest a potential role of the Dps proteins in zinc detoxification mechanisms involving the second zinc-binding site. 相似文献
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Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease. 相似文献
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Protein chains make numerous returns in globules, thus forming loops, closed by tight residue-to-residue contacts-closed loops. Previous statistical analysis of the sizes and locations of the closed loops in all major protein folds revealed that the loops have an almost standard contour length of 25-30 amino acid residues and follow one after another along the chain. In this work the closed loops of the major folds are presented in three dimensions. A special image filtering procedure is introduced that allows one to visualize the standard size closed loops for the first time. The loop positions along the sequences are verified by detection of loop-end clusters. 相似文献
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Prashath Karunaraj Olivia Tidswell Elizabeth J Duncan Mackenzie R Lovegrove Grace Jefferies Travis K Johnson Caroline W Beck Peter K Dearden 《Genetics》2022,221(1)
Noggin is an extracellular cysteine knot protein that plays a crucial role in vertebrate dorsoventral patterning. Noggin binds and inhibits the activity of bone morphogenetic proteins via a conserved N-terminal clip domain. Noncanonical orthologs of Noggin that lack a clip domain (“Noggin-like” proteins) are encoded in many arthropod genomes and are thought to have evolved into receptor tyrosine kinase ligands that promote Torso/receptor tyrosine kinase signaling rather than inhibiting bone morphogenic protein signaling. Here, we examined the molecular function of noggin/noggin-like genes (ApNL1 and ApNL2) from the arthropod pea aphid using the dorso-ventral patterning of Xenopus and the terminal patterning system of Drosophila to identify whether these proteins function as bone morphogenic protein or receptor tyrosine kinase signaling regulators. Our findings reveal that ApNL1 from the pea aphid can regulate both bone morphogenic protein and receptor tyrosine kinase signaling pathways, and unexpectedly, that the clip domain is not essential for its antagonism of bone morphogenic protein signaling. Our findings indicate that ancestral noggin/noggin-like genes were multifunctional regulators of signaling that have specialized to regulate multiple cell signaling pathways during the evolution of animals. 相似文献
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The ADP-ribosylation factor (Arf) Arf GTPase-activating proteins (GAPs) are a family of proteins that induce hydrolysis of GTP bound to Arf. A conserved domain containing a zinc finger motif mediates catalysis. The substrate, Arf.GTP, affects membrane trafficking and actin remodelling. Consistent with activity as an Arf regulator, the Arf GAPs affect both of these pathways. However, the Arf GAPs are likely to have Arf-independent activities that contribute to their cellular functions. Structures of the Arf GAPs are diverse containing catalytic, protein-protein interaction and lipid interaction domains in addition to the Arf GAP domain. Some Arf GAPs have been identified and characterized on the basis of activities other than Arf GAP. Here, we describe the Arf GAP family, enzymology of some members of the Arf GAP family and known functions of the proteins. The results discussed illustrate roles for both Arf-dependent and -independent activities in the regulation of cellular architecture. 相似文献
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The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132–amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1–dependent manner. This domain, coupled to nickel nitrilotriacetic acid (Ni-NTA) agarose beads, specifically recruited F-actin in the presence of CFL-1 and, when expressed in HeLa cells, inhibited Ca2+ entry into the TGN and secretory cargo sorting. Mutagenesis of four amino acids in SPCA1 that represent the CFL-1 binding site also affected Ca2+ import into the TGN and secretory cargo sorting. Altogether, our findings reveal the mechanism of CFL-1–dependent recruitment of actin to SPCA1 and the significance of this interaction for Ca2+ influx and secretory cargo sorting. 相似文献
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John S. Mattick 《EMBO reports》2001,2(11):986-991
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Roy S Gupta S Das S Sekar K Chatterji D Vijayan M 《Journal of molecular biology》2004,339(5):1103-1113
The structure of the DNA binding protein from starved cells from Mycobacterium smegmatis has been determined in three crystal forms and has been compared with those of similar proteins from other sources. The dodecameric molecule can be described as a distorted icosahedron. The interfaces among subunits are such that the dodecameric molecule appears to have been made up of stable trimers. The situation is similar in the proteins from Escherichia coli and Agrobacterium tumefaciens, which are closer to the M.smegmatis protein in sequence and structure than those from other sources, which appear to form a dimer first. Trimerisation is aided in the three proteins by the additional N-terminal stretches that they possess. The M.smegmatis protein has an additional C-terminal stretch compared to other related proteins. The stretch, known to be involved in DNA binding, is situated on the surface of the molecule. A comparison of the available structures permits a delineation of the rigid and flexible regions in the molecule. The subunit interfaces around the molecular dyads, where the ferroxidation centres are located, are relatively rigid. Regions in the vicinity of the acidic holes centred around molecular 3-fold axes, are relatively flexible. So are the DNA binding regions. The crystal structures of the protein from M.smegmatis confirm that DNA molecules can occupy spaces within the crystal without disturbing the arrangement of the protein molecules. However, contrary to earlier suggestions, the spaces do not need to be between layers of protein molecules. The cubic form provides an arrangement in which grooves, which could hold DNA molecules, criss-cross the crystal. 相似文献