共查询到20条相似文献,搜索用时 15 毫秒
1.
Robert Renthal 《Cellular and molecular life sciences : CMLS》2010,67(7):1077-1088
Polytopic α-helical membrane proteins cannot spontaneously insert into lipid bilayers without assistance from polytopic α-helical
membrane proteins that already reside in the membrane. This raises the question of how these proteins evolved. Our current
knowledge of the insertion of α-helices into natural and model membranes is reviewed with the goal of gaining insight into
the evolution of membrane proteins. Topics include: translocon-dependent membrane protein insertion, antibiotic peptides and
proteins, in vitro insertion of membrane proteins, chaperone-mediated insertion of transmembrane helices, and C-terminal tail-anchored
(TA) proteins. Analysis of the E. coli genome reveals several predicted C-terminal TA proteins that may be descendents of proteins involved in pre-cellular membrane
protein insertion. Mechanisms of pre-translocon polytopic α-helical membrane protein insertion are discussed. 相似文献
2.
Three-dimensional structure of annexins 总被引:4,自引:0,他引:4
Annexins constitute a family of structurally related calcium- and phospholipid-binding proteins whose molecular structure
has been investigated in detail in the crystalline and membrane-bound form. Their polypeptide chain is folded into four or
eight α-helical domains of similar structure with a central hydrophilic pore. Bound to phospholipid membranes, the four-domain arrangement
of the annexin molecule is conserved. A peripheral binding mode has been well documented by electron microscopy and a variety
of other techniques. 相似文献
3.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
4.
Dirk M. Walther Doron Rapaport Jan Tommassen 《Cellular and molecular life sciences : CMLS》2009,66(17):2789-2804
Membrane-embedded β-barrel proteins span the membrane via multiple amphipathic β-strands arranged in a cylindrical shape.
These proteins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. This situation is
thought to reflect the evolutionary origin of mitochondria and chloroplasts from Gram-negative bacterial endosymbionts. β-barrel
proteins fulfil a variety of functions; among them are pore-forming proteins that allow the flux of metabolites across the
membrane by passive diffusion, active transporters of siderophores, enzymes, structural proteins, and proteins that mediate
protein translocation across or insertion into membranes. The biogenesis process of these proteins combines evolutionary conservation
of the central elements with some noticeable differences in signals and machineries. This review summarizes our current knowledge
of the functions and biogenesis of this special family of proteins. 相似文献
5.
Maarten Moes Johannes Boonstra Elsa Regan-Klapisz 《Cellular and molecular life sciences : CMLS》2010,67(9):1547-1557
Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways
that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics
also activate cPLA2α. Moreover, arachidonic acid, the product of cPLA2α activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA2α plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon
stimulation of ruffling and cell migration by growth factors, endogenous cPLA2α and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane
dynamics. Inhibition of cPLA2α activity with specific inhibitors blocked growth factor-induced membrane and actin dynamics, suggesting an important role
for cPLA2α in these processes. 相似文献
6.
Nadja Mannowetz Sabine Kartarius Gunther Wennemuth Mathias Montenarh 《Cellular and molecular life sciences : CMLS》2010,67(22):3905-3913
Protein kinase CK2 is an ubiquitously expressed enzyme that is absolutely necessary for the survival of cells. Besides the
holoenzyme consisting of the regulatory β-subunit and the catalytic α- or α′-subunit, the subunits exist in separate forms.
The subunits bind to a number of other cellular proteins. We show the expression of individual subunits as well as interaction
with the transitional nuclear protein TNP1 and with the motor neuron protein KIF5C during spermatogenesis. TNP1 is a newly
identified binding partner of the α-subunit of CK2. CK2α and KIF5C were found in late spermatogenesis, whereas CK2β and TNP1
were found in early spermatogenesis. CK2α, CK2α′, TNP1, and KIF5C were detected in the acrosome of spermatozoa, while CK2β
was detectable in the mid-piece. Combinations of CK2 subunits might determine interactions with other proteins during spermatogenesis.
KIF5C as a kinesin motor neuron protein is probably involved in the redistribution of proteins during spermatogenesis. 相似文献
7.
Jean-Baptiste G Yang Z Greenwood MT 《Cellular and molecular life sciences : CMLS》2006,63(17):1969-1985
Regulator of G-Protein Signaling (RGS) refers to a conserved 120–125 amino acid motif that was first identified by its ability
to negatively regulate G-Protein-Coupled Receptor (GPCR) signalling. Mechanistically, RGSs were found to regulate GPCR responses
by binding to and stimulating the GTPase activity of the receptor-activated GTP-bound G α subunits. There are now over 25
mammalian RGSs containing proteins that are reported to carry out a variety of functions, many of which are unrelated to GPCR
signalling. RGS proteins range in size from small proteins that contain little more than an RGS box to very large proteins
that contain a variety of domains. The selectivity of function of the RGS proteins is attributable to the divergence of the
RGS sequences as well as the presence of a variety of functional motifs, which allow them to interact with other proteins.
Here we focus on the RGSs that are involved in modulating GPCR signalling by reviewing the diversity of the mechanisms involved
in regulating these RGSs.
Received 9 February 2006; received after revision 4 May 2006; accepted 22 May 2006 相似文献
8.
Signal regulation by family conspiracy 总被引:6,自引:0,他引:6
The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two
subgroups: SIRPα and SIRPβ, containing more than ten members. SIRPα has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors.
This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which
recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRPα may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRPβ subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP).
DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRPβ to activating machinery. SIRPα and SIRPβ thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus.
Received 6 July 2000; revised 2 August 2000; accepted 5 August 2000 相似文献
9.
The ATP-binding cassette family is one of the largest groupings of membrane proteins, moving allocrites across lipid membranes,
using energy from ATP. In bacteria, they reside in the inner membrane and are involved in both uptake and export. In eukaryotes,
these transporters reside in the cell’s internal membranes as well as in the plasma membrane and are unidirectional—out of
the cytoplasm. The range of substances that these proteins can transport is huge, which makes them interesting for structure–function
studies. Moreover, their abundance in nature has made them targets for structural proteomics consortia. There are eight independent
structures for ATP-binding cassette transporters, making this one of the best characterised membrane protein families. Our
understanding of the mechanism of transport across membranes and membrane protein structure in general has been enhanced by
recent developments for this family. 相似文献
10.
Parihar MS Parihar A Fujita M Hashimoto M Ghafourifar P 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1272-1284
α-Synuclein is a neuron-specific protein that contributes to the pathology of Parkinson’s disease via mitochondria-related mechanisms. The present study investigated possible interaction of α-synuclein with mitochondria and
consequences of such interaction. Using SHSY cells overexpressing α-synuclein A53T mutant or wild-type, as well as isolated
rat brain mitochondria, the present study shows that α-synuclein localizes at the mitochondrial membrane. In both SHSY cells
and isolated mitochondria, interaction of α-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings
suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by α-synuclein.
Received 27 December 2007; received after revision 7 February 2008; accepted 8 February 2008 相似文献
11.
Trimeric guanine nucleotide-binding proteins (G proteins) function as the key regulatory elements in a number of transmembrane
signaling cascades where they convey information from agonist-activated receptors to effector molecules. The subcellular localization
of G proteins is directly related to their functional role, i.e., the dominant portion of the cellular pool of G proteins
resides in the plasma membrane. An intimate association of G protein subunits with the plasma membrane has been well known
for a long time. However, results of a number of independent studies published in the past decade have indicated clearly that
exposure of intact target cells to agonists results in subcellular redistribution of the cognate G proteins from plasma membranes
to the light-vesicular membrane fractions, in internalization from the cell surface into the cell interior and in transfer
from the membrane to the soluble cell fraction (high-speed supernatant), i.e., solubilization. Solubilization of G protein
α subunits as a consequence of stimulation of G protein-coupled receptors (GPCRs) with agonists has also been observed in
isolated membrane preparations. The membrane-cytosol shift of G proteins was detected even after direct activation of these
proteins by non-hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In addition, prolonged stimulation
of GPCRs with agonists has been shown to lead to down-regulation of the relevant G proteins. Together, these data suggest
that G proteins might potentially participate in a highly complex set of events, which are generally termed desensitization
of the hormone response. Internalization, subcellular redistribution, solubilization, and down-regulation of trimeric G proteins
may thus provide an additional means (i.e., beside receptor-based mechanisms) to dampen the hormone or neurotransmitter response
after sustained (long-term) exposure.
Received 31 August 2001; received after revision 31 October 2001; accepted 7 November 2001 相似文献
12.
Small heat shock proteins: molecular structure and chaperone function 总被引:17,自引:0,他引:17
Small heat shock proteins (sHSPs) associate with nuclei, cytoskeleton and membranes, and as molecular chaperones they bind
partially denatured proteins, thereby preventing irreversible protein aggregation during stress. sHSP monomers consist of
a conserved α-crystallin domain of approximately 90 amino acid residues, bordered by variable amino- and carboxy-terminal
extensions. The sHSPs undergo dynamic assembly into mono- and poly-disperse oligomers where the rate of disassembly affects
chaperoning. The α-crystallin domain contains several β-strands organized into two β-sheets responsible for dimer formation,
the basic building block of most sHSPS. The amino-terminal extension modulates oligomerization, subunit dynamics and substrate
binding, whereas the flexible carboxy-terminal extension promotes solubility, chaperoning and oligomerization, the latter
by inter-subunit linkage. Crystallization studies have revealed sHSP structure and function. Additionally, site-directed mutagenesis,
biophysical investigations, functional studies and the discovery of relationships between mutated sHSPs and diseases have
illuminated the role of sHSP within cells.
Received 8 May 2005; received after revision 24 June 2005; accepted 19 July 2005 相似文献
13.
Ligand recognition by the I domain-containing integrins 总被引:11,自引:0,他引:11
Seven of the integrin α subunits described to date, α
1 , α
2 , α
L , α
X , α
d , α
M and α
E , contain a highly conserved I (or A) domain of approximately 200 amino acid residues inserted near the amino-terminus of
the subunit. As the result of a variety of independent experimental approaches, a large body of data has recently accumulated
that indicates that the I domains are independent, autonomously folding domains capable of directly binding ligands that play
a necessary and important role in ligand binding by the intact integrins. Recent crystallographic studies have elucidated
the structures of recombinant α
M and α
L I domains and also delineated a novel divalent cation-binding motif within the I domains (metal ion-dependent adhesion site,
MIDAS) that appears to mediate the divalent cation binding of the I domains and the I domain-containing integrins to their
ligands. 相似文献
14.
James R. Docherty 《Cellular and molecular life sciences : CMLS》2010,67(3):405-417
In this review, subtypes of functional α1-adrenoceptor are discussed. These are cell membrane receptors, belonging to the
seven-transmembrane-spanning G-protein-linked family of receptors, which respond to the physiological agonist noradrenaline.
α1-Adrenoceptors can be divided into α1A-, α1B- and α1D-adrenoceptors, all of which mediate contractile responses involving
Gq/11 and inositol phosphate turnover. A fourth α1-adrenoceptor, the α1L-, represents a functional phenotype of the α1A-adrenoceptor.
α1-Adrenoceptor subtype knock-out mice have refined our knowledge of the functions of α-adrenoceptor subtypes, particuarly
as subtype-selective agonists and antagonists are not available for all subtypes. α1-Adrenoceptors function as stimulatory
receptors involved particularly in smooth muscle contraction, especially contraction of vascular smooth muscle, both in local
vasoconstriction and in the control of blood pressure and temperature, and contraction of the prostate and bladder neck. Central
actions are now being elucidated. 相似文献
15.
Eleonora Dondossola Anna Gasparri Angela Bachi Renato Longhi Marie-Hélène Metz-Boutigue Bruno Tota Karen B. Helle Flavio Curnis Angelo Corti 《Cellular and molecular life sciences : CMLS》2010,67(12):2107-2118
Fibroblast adhesion can be modulated by proteins released by neuroendocrine cells and neurons, such as chromogranin A (CgA)
and its N-terminal fragment vasostatin-1 (VS-1, CgA1–78). We have investigated the mechanisms of the interaction of VS-1 with fibroblasts and of its pro-adhesive activity and have
found that the proadhesive activity of VS-1 relies on its interaction with the fibroblast membrane via a phospholipid-binding
amphipathic α-helix located within residues 47–66, as well as on the interaction of the adjacent C-terminal region 67–78,
which is structurally similar to ezrin–radixin–moesin-binding phosphoprotein 50 (a membrane-cytoskeleton adapter protein),
with other cellular components critical for the regulation of cell cytoskeleton. 相似文献
16.
Anna Maria Frassanito Laura Barsanti Vincenzo Passarelli Valtere Evangelista Paolo Gualtieri 《Cellular and molecular life sciences : CMLS》2010,67(6):965-971
Here, we report the DNA sequence of the rhodopsin gene in the alga Cyanophora paradoxa (Glaucophyta). The primers were designed according to the conserved regions of prokaryotic and eukaryotic rhodopsin-like
proteins deposited in the GenBank. The sequence consists of 1,272 bp comprised of 5 introns. The correspondent protein, named
Cyanophopsin, showed high identity to rhodopsin-like proteins of Archea, Bacteria, Fungi, and Algae. At the N-terminal, the
protein is characterized by a region with no transmembrane α-helices (80 aa), followed by a region with 7α-helices (219 aa)
and a shorter 35-aa C-terminal region. The DNA sequence of the N-terminal region was expressed in E. coli and the recombinant purified peptide was used as antigen in hens to obtain polyclonal antibodies. Indirect immunofluorescence
in C. paradoxa cells showed a marked labeling of the muroplast (aka cyanelle) membrane. 相似文献
17.
The parvins 总被引:5,自引:0,他引:5
The parvins are a family of proteins involved in linking integrins and associated proteins with intracellular pathways that
regulate actin cytoskeletal dynamics and cell survival. Both α-parvin (PARVA) and β-parvin (PARVB) localize to focal adhesions
and function in cell adhesion, spreading, motility and survival through interactions with partners, such as integrin-linked
kinase (ILK), paxillin, α-actinin and testicular kinase 1. A complex of PARVA with ILK and the LIM protein PINCH-1 is critical
for cell survival in a variety of cells, including certain cancer cells, kidney podocytes and cardiac myocytes. While PARVA
inhibits the activities of Rac1 and testicular kinase 1 and cell spreading, PARVB binds αPIX and α-actinin, and can promote
cell spreading. In contrast to PARVA, PARVB inhibits ILK activity and reverses some of its oncogenic effects in cancer cells.
This review focuses on the structure and function of the parvins and some possible roles in human diseases.
Received 5 August 2005; received after revision 5 September 2005; accepted 22 September 2005 相似文献
18.
The compositional difference in microbial and human cell membranes allows antimicrobial peptides to preferentially bind microbes.
Peptides which specifically target lipopolysaccharide (LPS) and palmitoyl-oleoyl-phosphatidylglycerol (POPG) are efficient
antibiotics. From the core LPS-binding region of Factor C, two 34-mer Sushi peptides, S1 and S3, were derived. S1 functions
as a monomer, while S3 is active as a dimer. Both S1 and S3 display detergent-like properties in disrupting LPS aggregates,
with specificity for POPG resulting from electrostatic and hydrophobic forces between the peptides and the bacterial lipids.
During interaction with POPG, the S1 transitioned from a random coil to an α-helix, while S3 resumed a mixture of α-helix
and β-sheet structures. The unsaturated nature of POPG confers fluidity and enhances insertion of the peptides into the lipid
bilayer, causing maximal disruption of the bacterial membrane. These parameters should be considered in designing and developing
new generations of peptide antibiotics with LPS-neutralizing capability.
Received 2 October 2007; received after revision 2 November 2007; accepted 4 December 2007
J. L. Ding, B. Ho: Co-senior authors. 相似文献
19.
The application of fractal dimension-based constructs to probe the protein interior dates back to the development of the concept
of fractal dimension itself. Numerous approaches have been tried and tested over a course of (almost) 30 years with the aim
of elucidating the various facets of symmetry of self-similarity prevalent in the protein interior. In the last 5 years especially,
there has been a startling upsurge of research that innovatively stretches the limits of fractal-based studies to present
an array of unexpected results on the biophysical properties of protein interior. In this article, we introduce readers to
the fundamentals of fractals, reviewing the commonality (and the lack of it) between these approaches before exploring the
patterns in the results that they produced. Clustering the approaches in major schools of protein self-similarity studies,
we describe the evolution of fractal dimension-based methodologies. The genealogy of approaches (and results) presented here
portrays a clear picture of the contemporary state of fractal-based studies in the context of the protein interior. To underline
the utility of fractal dimension-based measures further, we have performed a correlation dimension analysis on all of the
available non-redundant protein structures, both at the level of an individual protein and at the level of structural domains.
In this investigation, we were able to separately quantify the self-similar symmetries in spatial correlation patterns amongst
peptide–dipole units, charged amino acids, residues with the π-electron cloud and hydrophobic amino acids. The results revealed
that electrostatic environments in the interiors of proteins belonging to ‘α/α toroid’ (all-α class) and ‘PLP-dependent transferase-like’
domains (α/β class) are highly conducive. In contrast, the interiors of ‘zinc finger design’ (‘designed proteins’) and ‘knottins’
(‘small proteins’) were identified as folds with the least conducive electrostatic environments. The fold ‘conotoxins’ (peptides)
could be unambiguously identified as one type with the least stability. The same analyses revealed that peptide–dipoles in
the α/β class of proteins, in general, are more correlated to each other than are the peptide–dipoles in proteins belonging
to the all-α class. Highly favorable electrostatic milieu in the interiors of TIM-barrel, α/β-hydrolase structures could explain
their remarkably conserved (evolutionary) stability from a new light. Finally, we point out certain inherent limitations of
fractal constructs before attempting to identify the areas and problems where the implementation of fractal dimension-based
constructs can be of paramount help to unearth latent information on protein structural properties. 相似文献
20.
Conlon JM 《Cellular and molecular life sciences : CMLS》2011,68(13):2303-2315
Cationic peptides that adopt an amphipathic α-helical conformation in a membrane-mimetic environment are synthesized in the
skins of many frog species. These peptides often display cytolytic activities against bacteria and fungi consistent with the
idea that they play a role in the host’s system of defense against pathogenic microorganisms, but their importance in the
survival strategy of the animal is not clearly understood. Despite the common misconception that antimicrobial peptides are
synthesized in the skins of all anurans, the species distribution is sporadic, suggesting that their production may confer
some evolutionary advantage to the organism but is not necessary for survival. The low potency of many frog skin antimicrobial
peptides is consistent with the hypothesis that cutaneous symbiotic bacteria may provide the major system of defense against
pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species. 相似文献