共查询到20条相似文献,搜索用时 359 毫秒
1.
Diverse molecular functions of Hu proteins 总被引:1,自引:1,他引:0
2.
Proliferating cell nuclear antigen: a proteomics view 总被引:3,自引:0,他引:3
Naryzhny SN 《Cellular and molecular life sciences : CMLS》2008,65(23):3789-3808
Proliferating cell nuclear antigen (PCNA), a cell cycle marker protein, is well known as a DNA sliding clamp for DNA polymerase
delta and as an essential component for eukaryotic chromosomal DNA replication and repair. Due to its mobility inside nuclei,
PCNA is dynamically presented in a soluble or chromatin-associated form. The heterogeneity and specific modifications of PCNA
may reflect its multiple functions and the presence of many binding partners in the cell. The recent proteomics approaches
applied to characterizing PCNA interactions revealed multiple PCNA partners with a wide spectrum of activity and unveiled
the possible existence of new PCNA functions. Since more than 100 PCNA-interacting proteins and several PCNA modifications
have already been reported, a proteomics point of view seems exactly suitable to better understand the role of PCNA in cellular
functions.
Received 29 May 2008; received after revision 7 July 2008; accepted 16 July 2008 相似文献
3.
Metallomics and metalloproteomics 总被引:1,自引:0,他引:1
Metallomics and metalloproteomics are emerging fields addressing the role, uptake, transport and storage of trace metals essential
for protein functions. The methodologies utilized in metallomics and metalloproteomics to provide information on the identity,
quantity and function of metalloproteins are discussed. The most widely used approach is through inductively coupled plasma
mass spectrometry to identify the metal bound to a protein, and electrospray ionization mass spectrometry to elucidate the
structure, dynamics and function of a metal-protein complex. Other approaches include X-ray absorption and X-ray fluorescence
spectroscopies, and bioinformatics sequence analysis. X-ray absorption spectroscopy utilizing a synchrotron radiation source
is a powerful tool to provide a direct analysis of metal bound to proteins and proteomic metal distribution in biological
matrices. With the advent of genome sequencing, a large database of protein primary structures has been established, and specific
tools to identify metalloproteins in the genome sequences have been developed.
Received 8 April 2008; received after revision 12 May 2008; accepted 15 May 2008 相似文献
4.
Lundstrom K 《Cellular and molecular life sciences : CMLS》2006,63(22):2597-2607
Structure-based drug discovery has proven useful in improving and shortening the drug development process. The approach of
structural genomics to study a large number of targets in parallel has been commonly applied to protein families and even
whole genomes. Paradoxically, although membrane proteins represent the largest type of drug targets, up to 70% today, determination
of their structure has been modest compared to that of soluble proteins. Because membrane proteins are important for drug
discovery an emphasis has been placed on developing technologies and methods to determine membrane protein structures. Several
structural genomics initiatives have been established, focusing on the structural biology of membrane proteins.
Received 31 May 2006; received after revision 5 July 2006; accepted 9 August 2006 相似文献
5.
The activation and signalling activity of the membrane μ-opioid receptor (MOP-R) involve interactions among the receptor,
G-proteins, effectors and many other membrane or cytosolic proteins. Decades of investigation have led to identification of
the main biochemical processes, but the mechanisms governing the successive protein–protein interactions have yet to be established.
We will need to unravel the dynamic membrane organisation of this complex and multifaceted molecular machinery if we are to
understand these mechanisms. Here, we review and discuss advances in our understanding of the signalling mechanism of MOP-R
resulting from biochemical or biophysical studies of the organisation of this receptor in the plasma membrane. 相似文献
6.
Ronda Bransteitter Courtney Prochnow Xiaojiang S. Chen 《Cellular and molecular life sciences : CMLS》2009,66(19):3137-3147
The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases has emerged as an intensively
studied field as a result of their important biological functions. These enzymes are involved in lipid metabolism, antibody
diversification, and the inhibition of retrotransposons, retroviruses, and some DNA viruses. The APOBEC proteins function
in these roles by deaminating single-stranded (ss) DNA or RNA. There are two high-resolution crystal structures available
for the APOBEC family, Apo2 and the C-terminal catalytic domain (CD2) of Apo3G or Apo3G-CD2 [Holden et al. (Nature 456:121–124,
2008); Prochnow et al. (Nature 445:447–451, 2007)]. Additionally, the structure of Apo3G-CD2 has also been determined using
NMR [Chen et al. (Nature 452:116–119, 2008); Furukawa et al. (EMBO J 28:440–451, 2009); Harjes et al. (J Mol Biol, 2009)].
A detailed structural analysis of the APOBEC proteins and a comparison to other zinc-coordinating deaminases can facilitate
our understanding of how APOBEC proteins bind nucleic acids, recognize substrates, and form oligomers. Here, we review the
recent development of structural and functional studies that apply to Apo3G as well as the APOBEC deaminase family. 相似文献
7.
p63 in epithelial development 总被引:2,自引:0,他引:2
Candi E Cipollone R Rivetti di Val Cervo P Gonfloni S Melino G Knight R 《Cellular and molecular life sciences : CMLS》2008,65(20):3126-3133
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10.
Symmetric DNA sequence motifs allow the formation of palindromic protein/DNA complexes. Although symmetric protein sequence
motifs are less common, recent structural discoveries have unraveled a few protein/protein complexes with palindromic symmetry.
Remarkably, symmetric protein/protein complexes can be generated either by adjacent or remote sequence motifs, which may be
repeated or inverted. This contribution reflects and comments on recent findings of palindromic protein/protein complexes.
Received 14 May 2008; received after revision 21 June 2008; accepted 14 July 2008 相似文献
11.
Endogenous opioids have been studied extensively since their discovery, in the hope of finding a perfect analgesic, devoid
of the secondary effects of alkaloid opioids. However, the design of selective opioid agonists has proved very difficult.
First, structural studies of peptides in general are hampered by their intrinsic flexibility. Second, the relationship between
constitution and the so-called 'bioactive conformation' is far from obvious. Ideally, a direct structural study of the complex
between a peptide and its receptor should answer both questions, but such a study is not possible, because opioid receptors
are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid
peptides are still important for drug design and also for indirect receptor mapping. This review deals with conformational
studies of natural opioid peptides in several solvents that mimic in part the different environments in which the peptides
exert their action. None of the structural investigations yields a convincing bioactive conformation, but the global conformation
of longer peptides in biomimetic environments can shed light on the interaction with receptors.
Received 15 April 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献
12.
Sarramegn V Muller I Milon A Talmont F 《Cellular and molecular life sciences : CMLS》2006,63(10):1149-1164
G protein-coupled receptors (GPCRS) represent a class of integral membrane proteins involved in many biological processes
and pathologies. Fifty percent of all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to target
GPCRs. Despite these crucial biological implications, very little is known, at atomic resolution, about the detailed molecular
mechanisms by which these membrane proteins are able to recognize their extra-cellular stimuli and transmit the associated
messages. Obviously, our understanding of GPCR functioning would be greatly facilitated by the availability of high-resolution
three-dimensional (3D) structural data. However, expression, solubilization and purification of these membrane proteins are
not easy to achieve, and at present, only one 3D structure has been determined, that of bovine rhodopsin. This review presents
and compares the different successful strategies which have been applied to solubilize and purify recombinant GPCRs in the
perspective of structural biology experiments.
Received 21 November 2005; received after revision 20 January 2006; accepted 2 February 2006
An erratum to this article is available at . 相似文献
13.
Jung-Eun Park Nak-Kyun Soung Yoshikazu Johmura Young H. Kang Chenzhong Liao Kyung H. Lee Chi Hoon Park Marc C. Nicklaus Kyung S. Lee 《Cellular and molecular life sciences : CMLS》2010,67(12):1957-1970
Members of the polo subfamily of protein kinases have emerged as important regulators in diverse aspects of the cell cycle
and cell proliferation. A large body of evidence suggests that a highly conserved polo-box domain (PBD) present in the C-terminal
non-catalytic region of polo kinases plays a pivotal role in the function of these enzymes. Recent advances in our comprehension
of the mechanisms underlying mammalian polo-like kinase 1 (Plk1)-dependent protein–protein interactions revealed that the
PBD serves as an essential molecular mediator that brings the kinase domain of Plk1 into proximity with its substrates, mainly
through phospho-dependent interactions with its target proteins. In this review, current understanding of the structure and
functions of PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other phospho-independent functions
of PBD are discussed. 相似文献
14.
Tetratricopeptide repeats (TPRs) are loosely conserved 34-amino acid sequence motifs that have been shown to function as scaffolding structures to mediate protein-protein interactions. TPRs have been identified in a number of proteins with diverse functions and cellular locations. Recent studies suggest that individual TPR motifs can confer specificity in promoting homotypic and/or heterotypic interactions, often in a mutually exclusive manner. These features are best exemplified by the P58IPK protein, an influenza virus-activated cellular inhibitor of the PKR protein kinase, whose different TPR motifs mediate interactions with distinct proteins. P58IPK, which possesses cochaperone and oncogenic properties, represents a unique class of TPR proteins containing a J-domain. Here we review recent progress on the structural and functional characterization of P58IPK, and discuss the possible mechanisms by which P58IPK modulates PKR and induces tumorigenesis in view of present knowledge of TPR proteins and molecular chaperones. 相似文献
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16.
Bitter peptides and bitter taste receptors 总被引:1,自引:0,他引:1
Bitter peptides are a structurally diverse group of oligopeptides often generated in fermented, aged, and hydrolyzed food
products that make them unfavorable for consumption. Humans perceive bitterness by a repertoire of 25 human bitter receptors,
termed T2Rs. Knowledge of the structural features of bitter receptors and of the factors that stimulate bitter receptors will
aid in understanding the mechanism responsible for bitter taste perception. This article reviews the current knowledge regarding
structural features of bitter peptides and bitter taste receptors.
Received 24 November 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
17.
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
18.
Ulrich Salzer Julius Kostan Kristina Djinović-Carugo 《Cellular and molecular life sciences : CMLS》2017,74(13):2413-2438
The BAR domain is the eponymous domain of the “BAR-domain protein superfamily”, a large and diverse set of mostly multi-domain proteins that play eminent roles at the membrane cytoskeleton interface. BAR domain homodimers are the functional units that peripherally associate with lipid membranes and are involved in membrane sculpting activities. Differences in their intrinsic curvatures and lipid-binding properties account for a large variety in membrane modulating properties. Membrane activities of BAR domains are further modified and regulated by intramolecular or inter-subunit domains, by intermolecular protein interactions, and by posttranslational modifications. Rather than providing detailed cell biological information on single members of this superfamily, this review focuses on biochemical, biophysical, and structural aspects and on recent findings that paradigmatically promote our understanding of processes driven and modulated by BAR domains. 相似文献
19.
A. Fridkin A. Penkner V. Jantsch Y. Gruenbaum 《Cellular and molecular life sciences : CMLS》2009,66(9):1518-1533
20.
Phylogenetic distribution, functional epitopes and evolution of the CSαβ superfamily 总被引:1,自引:1,他引:0
A superfamily of proteins often conserves a common structural scaffold but develops diverse biochemical and biological functions during evolution. The understanding of evolutionary mechanisms responsible for this diversity is of fundamental importance not only in structural genomics but also in nature-guided drug design. A superfamily of peptides with a conserved CSalphabeta structural motif provides a considerably intriguing example to approach such an issue. The peptides from this superfamily have wide origins, ranging from plants to animals, and exhibit diverse biological activities, varying from a sweet-tasting protein to antibacterial defensins and animal toxins targeting ion channels. This review describes the phylogenetic distribution and structural classifi cation of this unique scaffold and provides new insights into its functional diversity from the perspective of sequence, structure and evolution. 相似文献