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1.
BAR domain superfamily proteins have emerged as central regulators of dynamic membrane remodeling, thereby playing important
roles in a wide variety of cellular processes, such as organelle biogenesis, cell division, cell migration, secretion, and
endocytosis. Here, we review the mechanistic and structural basis for the membrane curvature-sensing and deforming properties
of BAR domain superfamily proteins. Moreover, we summarize the present state of knowledge with respect to their regulation
by autoinhibitory mechanisms or posttranslational modifications, and their interactions with other proteins, in particular
with GTPases, and with membrane lipids. We postulate that BAR superfamily proteins act as membrane-deforming scaffolds that
spatiotemporally orchestrate membrane remodeling. 相似文献
2.
Charles A. Galea Hai M. Nguyen K. George Chandy Brian J. Smith Raymond S. Norton 《Cellular and molecular life sciences : CMLS》2014,71(7):1191-1210
MMP23 is a member of the matrix metalloprotease family of zinc- and calcium-dependent endopeptidases, which are involved in a wide variety of cellular functions. Its catalytic domain displays a high degree of structural homology with those of other metalloproteases, but its atypical domain architecture suggests that it may possess unique functional properties. The N-terminal MMP23 pro-domain contains a type-II transmembrane domain that anchors the protein to the plasma membrane and lacks the cysteine-switch motif that is required to maintain other MMPs in a latent state during passage to the cell surface. Instead of the C-terminal hemopexin domain common to other MMPs, MMP23 contains a small toxin-like domain (TxD) and an immunoglobulin-like cell adhesion molecule (IgCAM) domain. The MMP23 pro-domain can trap Kv1.3 but not closely-related Kv1.2 channels in the endoplasmic reticulum, preventing their passage to the cell surface, while the TxD can bind to the channel pore and block the passage of potassium ions. The MMP23 C-terminal IgCAM domain displays some similarity to Ig-like C2-type domains found in IgCAMs of the immunoglobulin superfamily, which are known to mediate protein–protein and protein–lipid interactions. MMP23 and Kv1.3 are co-expressed in a variety of tissues and together are implicated in diseases including cancer and inflammatory disorders. Further studies are required to elucidate the mechanism of action of this unique member of the MMP family. 相似文献
3.
Galat A 《Cellular and molecular life sciences : CMLS》2011,68(20):3437-3451
The transforming growth factor-β (TGFβ) superfamily of proteins and their receptors are crucial developmental factors for
all metazoan organisms. Cystine-knot (CK) motif is a spatial feature of the TGFβ superfamily of proteins whereas the extra-cellular
domains (ectodomains) of their respective receptors form three-fingered protein domain (TFPD), both stabilized by tight cystine
networks. Analyses of multiple sequence alignments of these two domains encoded in various genomes revealed that the cystines
forming the CK and TFPD folds are conserved, whereas the remaining polypeptide patches are diversified. Orthologues of the
human TGFβs and their respective receptors expressed in diverse vertebrates retain high sequence conservation. Examination
of 3D structures of various TGFβ factors bound to their receptors have revealed that the CK and TFPD domains display several
similar spatial traits suggesting that these two different protein folds might have been acquired from a common ancestor. 相似文献
4.
Tails of unconventional myosins 总被引:5,自引:0,他引:5
In addition to the conventional myosins (class II) required for processes such as muscle contraction and cytokinesis, the myosin superfamily of actin-based motor proteins includes at least 14 'unconventional' classes. These unconventional myosins are defined by myosin-like head (motor) domains attached to class-specific tail domains that differ greatly from those of myosin-II. The unconventional myosins account for almost two-thirds of the 28 or more myosin genes currently believed to be expressed in humans and 80-90% of the approximately 10 or more myosin genes expressed in a typical nonmuscle cell. Although these members of the myosin superfamily have not been as intensively investigated as the conventional myosins, unconventional myosins are known or believed to power many forms of actin-based motility and organelle trafficking. The presence of signaling domains such as kinase domains, SH3 domains, PH domains or GTPase-activating domains in the tails of unconventional myosins indicates that these proteins can also be components of signal transduction pathways. Since several classes of the myosin superfamily have been found only in lower eukaryotes or plants (VIII, XI, XIII and XIV), in this review we will focus on the structures and properties of the unconventional myosins found in multicellular animals (excluding classes I and V, which have been reviewed elsewhere recently). Special attention will be focused on the three classes of unconventional myosins that can cause deafness in mouse or humans when mutated. In addition, we discuss the discovery of a pair of intriguing domains, the Myosin Tail Homology 4 (MyTH4) and FERM (band 4.1, Ezrin, Radixin, Moesin) domains, that are present in the tails of otherwise very different myosins as well as a plant kinesin-like protein. Recent progress in the identification of novel unconventional myosins will also be summarized. 相似文献
5.
In eukaryotic cells membrane compartments are connected through cargo-selective vesicle trafficking mediating the exchange
of components between different organelles. This exchange is essential to maintain their structural integrity and specific
composition. A fundamental regulatory step in vesicle formation is the activation of small ARF GTPases by exchanging their
bound GDP for GTP, which is a prerequisite for ARF-mediated effector recruitment. Activation of ARFs is catalyzed by the characteristic
SEC7 domain of guanine nucleotide exchange factors (ARF-GEFs), which are classified according to their additional protein
domains.The only group of ARF-GEFs conserved in mammals, yeast and plants are the large ARF-GEFs. This review summarizes recent
findings on the function of large ARF-GEFs, and the use of the inhibitor Brefeldin A as a potent tool in understanding membrane
trafficking. Furthermore we highlight common themes and apparent differences in large ARF-GEF function between eukaryotic
kingdoms. 相似文献
6.
Adducin: structure, function and regulation 总被引:7,自引:0,他引:7
Adducin is a ubiquitously expressed membrane-skeletal protein localized at spectrin-actin junctions that binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in sequence and all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. The tail domains of all adducin subunits end with a highly conserved 22-residue myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that has homology to MARCKS protein. Adducin caps the fast-growing ends of actin filaments and also preferentially recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related domains are required for these activities. The neck domain self-associates to form oligomers. The MARCKS-related domain binds calmodulin and contains the major phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the kinase inhibit in vitro activities of adducin involving actin and spectrin. Recent observations suggest a role for adducin in cell motility, and as a target for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent physiological sites of regulation of adducin include dendritic spines of hippocampal neurons, platelets and growth cones of axons. 相似文献
7.
Gurunadh R. Chichili William Rodgers 《Cellular and molecular life sciences : CMLS》2009,66(14):2319-2328
Cell membranes are structurally heterogeneous, composed of discrete domains with unique physical and biological properties.
Membrane domains can form through a number of mechanisms involving lipid–lipid and protein–lipid interactions. One type of
membrane domain is the cholesterol-dependent membrane raft. How rafts form remains a current topic in membrane biology. We
review here evidence of structuring of rafts by the cortical actin cytoskeleton. This includes evidence that the actin cytoskeleton
associates with rafts, and that many of the structural and functional properties of rafts require an intact actin cytoskeleton.
We discuss the mechanisms of the actin-dependent raft organization, and the properties of the actin cytoskeleton in regulating
raft-associated signaling events. We end with a discussion of membrane rafts and the actin cytoskeleton in T cell activation,
which function synergistically to initiate the adaptive immune response. 相似文献
8.
Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain 总被引:1,自引:0,他引:1
Rivera-Milla E Stuermer CA Málaga-Trillo E 《Cellular and molecular life sciences : CMLS》2006,63(3):343-357
Reggies (flotillins) are detergent-resistant microdomains involved in the scaffolding of large heteromeric complexes that
signal across the plasma membrane. Based on the presence of an evolutionarily widespread motif, reggies/flotillins have been
included within the SPFH (stomatin-prohibitin-flotillin-HflC/K) protein superfamily. To better understand the origin and evolution
of reggie/flotillin structure and function, we searched databases for reggie/flotillin and SPFH-like proteins in organisms
at the base and beyond the animal kingdom, and used the resulting dataset to compare their structural and functional domains.
Our analysis shows that the SPFH grouping has little phylogenetic support, probably due to convergent evolution of its members.
We also find that reggie/flotillin homologues are highly conserved among metazoans but are absent in plants, fungi and bacteria,
where only proteins with ‘reggie-like’ domains can be found. However, despite their low sequence similarities, reggie/flotillin
and ‘reggie-like’ domains appear to subserve related functions, suggesting that their basic biological role was acquired independently
during evolution.
Received 21 September 2005; received after revision 14 November 2005; accepted 21 November 2005 相似文献
9.
Magnus Kjaergaard 《Cellular and molecular life sciences : CMLS》2017,74(17):3205-3224
Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine receptors. The functions of the disordered regions are many and varied. We will discuss selected examples including: (1) Organization of receptors, kinases, phosphatases and second messenger sources into signaling complexes. (2) Modulation of the membrane-embedded domain function by ball-and-chain like mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding protein disorder. 相似文献
10.
Lactoferricin 总被引:1,自引:0,他引:1
The peptide lactoferricin (Lfcin) can be released from the multifunctional protein lactoferrin (LF) through proteolysis by pepsin under acidic conditions, a reaction that occurs naturally in the stomach. Lfcin encompasses a large portion of the functional domain of the intact protein, and in many cases it not only retains the activities of LF but is more active. Lfcin possesses strong antimicrobial and weak antiviral activities, and it also has potent antitumor and immunological properties. This review covers the current state of research in this field, focusing on the many beneficial activities of this peptide. Throughout we will discuss the breadth of Lfcin activity as well as the mechanism of action. Many recent studies have drawn attention to the fact that the main site of action for the peptide may be intracellular. In addition the results of structural and dynamic studies of Lfcin are presented, and the relationship between structure and activity is explored. 相似文献
11.
Tim Steinbacher Daniel Kummer Klaus Ebnet 《Cellular and molecular life sciences : CMLS》2018,75(8):1393-1409
Cell adhesion molecules (CAMs) of the immunoglobulin superfamily (IgSF) regulate important processes such as cell proliferation, differentiation and morphogenesis. This activity is primarily due to their ability to initiate intracellular signaling cascades at cell–cell contact sites. Junctional adhesion molecule-A (JAM-A) is an IgSF-CAM with a short cytoplasmic tail that has no catalytic activity. Nevertheless, JAM-A is involved in a variety of biological processes. The functional diversity of JAM-A resides to a large part in a C-terminal PDZ domain binding motif which directly interacts with nine different PDZ domain-containing proteins. The molecular promiscuity of its PDZ domain motif allows JAM-A to recruit protein scaffolds to specific sites of cell–cell adhesion and to assemble signaling complexes at those sites. Here, we review the molecular characteristics of JAM-A, including its dimerization, its interaction with scaffolding proteins, and the phosphorylation of its cytoplasmic domain, and we describe how these characteristics translate into diverse biological activities. 相似文献
12.
The polycystins: a novel class of membrane-associated proteins involved in renal cystic disease 总被引:2,自引:0,他引:2
Sandford R Mulroy S Foggensteiner L 《Cellular and molecular life sciences : CMLS》1999,56(7-8):567-579
Polycystin-1, polycystin-2 and polycystin-L are the predicted protein products of the PKD1, PKD2 and PKDL genes, respectively.
Mutations in PKD1 and PKD2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). This
condition is one of the commonest mendelian disorders of man with a prevalence of 1:800 and is responsible for nearly 10%
of cases of end-stage renal failure in adults. The cloning of PKD1 and PKD2 in recent years has provided the initial steps
in defining the mechanisms underlying renal cyst formation in this condition, with the aim of defining pharmacological and
genetic interventions that may ameliorate the diverse and often serious clinical manifestations of this disease. The PKD genes
share regions of sequence similarity, and all predict integral membrane proteins. Whilst the predicted protein domain structure
of polycystin-1 suggests it is involved in cell-cell or cell-matrix interactions, the similarity of polycystin-2 and polycystin-L
to the pore-forming domains of some cation channels suggests that they all form subunits of a large plasma membrane ion channel.
In the few years since the cloning of the PKD genes, a consensus that defines the range of mutations, expression pattern,
interactions and functional domains of these genes and their protein products is emerging. This review will therefore attempt
to summarise these data and provide an insight in to the key areas in which polycystin research is unravelling the mechanisms
involved in renal cyst formation.
Received 22 February 1999; received after revision 5 July 1999; accepted 6 July 1999 相似文献
13.
Emilia Pedone Danila Limauro Katia D’Ambrosio Giuseppina De Simone Simonetta Bartolucci 《Cellular and molecular life sciences : CMLS》2010,67(22):3797-3814
The Thioredoxin (Trx) fold is a versatile protein scaffold consisting of a four-stranded β-sheet surrounded by three α-helices.
Various insertions are possible on this structural theme originating different proteins, which show a variety of functions
and specificities. During evolution, the assembly of different Trx fold domains has been used many times to build new multi-domain
proteins able to perform a large number of catalytic functions. To clarify the interaction mode of the different Trx domains
within a multi-domain structure and how their combination can affect catalytic performances, in this review, we report on
a structural and functional analysis of the most representative proteins containing more than one catalytically active Trx
domain: the eukaryotic protein disulfide isomerases (PDIs), the thermophilic protein disulfide oxidoreductases (PDOs) and
the hybrid peroxiredoxins (Prxs). 相似文献
14.
Anna Rising Mona Widhe Jan Johansson My Hedhammar 《Cellular and molecular life sciences : CMLS》2011,68(2):169-184
Spider dragline silk is an outstanding material made up of unique proteins—spidroins. Analysis of the amino acid sequences
of full-length spidroins reveals a tripartite composition: an N-terminal non-repetitive domain, a highly repetitive central
part composed of approximately 100 polyalanine/glycine rich co-segments and a C-terminal non-repetitive domain. Recent molecular
data on the terminal domains suggest that these have different functions. The composite nature of spidroins allows for recombinant
production of individual and combined regions. Miniaturized spidroins designed by linking the terminal domains with a limited
number of repetitive segments recapitulate the properties of native spidroins to a surprisingly large extent, provided that
they are produced and isolated in a manner that retains water solubility until fibre formation is triggered. Biocompatibility
studies in cell culture or in vivo of native and recombinant spider silk indicate that they are surprisingly well tolerated,
suggesting that recombinant spider silk has potential for biomedical applications. 相似文献
15.
Marcel Zámocký Bernhard Gasselhuber Paul G. Furtmüller Christian Obinger 《Cellular and molecular life sciences : CMLS》2014,71(23):4681-4696
Heme peroxidases and catalases are key enzymes of hydrogen peroxide metabolism and signaling. Here, the reconstruction of the molecular evolution of the peroxidase–catalase superfamily (annotated in pfam as PF00141) based on experimentally verified as well as numerous newly available genomic sequences is presented. The robust phylogenetic tree of this large enzyme superfamily was obtained from 490 full-length protein sequences. Besides already well-known families of heme b peroxidases arranged in three main structural classes, completely new (hybrid type) peroxidase families are described being located at the border of these classes as well as forming (so far missing) links between them. Hybrid-type A peroxidases represent a minor eukaryotic subfamily from Excavates, Stramenopiles and Rhizaria sharing enzymatic and structural features of ascorbate and cytochrome c peroxidases. Hybrid-type B peroxidases are shown to be spread exclusively among various fungi and evolved in parallel with peroxidases in land plants. In some ascomycetous hybrid-type B peroxidases, the peroxidase domain is fused to a carbohydrate binding (WSC) domain. Both here described hybrid-type peroxidase families represent important turning points in the complex evolution of the whole peroxidase–catalase superfamily. We present and discuss their phylogeny, sequence signatures and putative biological function. 相似文献
16.
The leucine-rich repeat structure 总被引:2,自引:0,他引:2
Bella J Hindle KL McEwan PA Lovell SC 《Cellular and molecular life sciences : CMLS》2008,65(15):2307-2333
The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures. 相似文献
17.
Bennasroune A Gardin A Auzan C Clauser E Dirrig-Grosch S Meira M Appert-Collin A Aunis D Crémel G Hubert P 《Cellular and molecular life sciences : CMLS》2005,62(18):2124-2131
Receptor tyrosine kinases play essential roles in cell proliferation and differentiation. We have recently shown that peptides corresponding to the transmembrane domains of the epidermal growth factor (EGF) and ErbB2 receptors inhibit their corresponding receptor activation in cancer cell lines. We extend this observation to cells transfected with chimeric insulin receptors where the transmembrane domain has been replaced by that of the EGF receptor or a mutated Erb2 domain. Peptides corresponding to the transmembrane domains of the EGF receptor and ErbB2 are able to inhibit specifically the autophosphorylation of insulin receptors with the corresponding domain. This inhibitory effect is correlated with the propensity of the different transmembrane domains to self-associate in a genetic reporter assay. Thus, our data strengthen the notion that transmembrane domains are involved in erbB receptor activation, and that these receptors can be modulated by inhibiting proteinprotein interactions within the membrane.Received 25 May 2005; received after revision 13 July 2005; accepted 22 July 2005 相似文献
18.
Llorca O 《Cellular and molecular life sciences : CMLS》2008,65(9):1302-1310
In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A2 receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains
in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like
domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional
implication. Recent research has revealed that several members of this family can exist in at least two configurations: an
extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation
where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational
transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization.
Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007 相似文献
19.
Wnt-frizzled signaling to G-protein-coupled effectors 总被引:2,自引:0,他引:2
20.
F Pattus D Massotte H U Wilmsen J Lakey D Tsernoglou A Tucker M W Parker 《Experientia》1990,46(2):180-192
Colicins are plasmid-encoded protein antibiotics which kill bacteria closely related to the producing strain (generally Escherichia coli). The study of the function of colicins has revealed many features which reflect common targeting and translocation mechanisms with bacteriophages and toxins. Like many toxins, colicins are composed of structural domains specialized in one of the different steps of the activity, targeting, translocation and killing. The major group comprises those colicins which permeabilize the cytoplasmic membrane, thereby destroying the cell's membrane potential. These colicins form well-defined voltage-gated ion channels in artificial membranes. The scope of this review is to describe some of the more recent findings concerning the structure and mode of action of pore-forming colicins with a special attention to models of membrane insertion and pore structure based on the recently determined three-dimensional structure of the pore-forming domain of colicin A. 相似文献