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1.
W. B. Upholt L. Chandrasekaran M. L. Tanzer 《Cellular and molecular life sciences : CMLS》1993,49(5):384-392
The large aggregating chondroitin sulfate proteoglycan of cartilage, aggrecan, has served as a prototype of proteoglycan structure. Molecular cloning has elucidated its primary structure and revealed both known and unknown domains. To date the complete structures of chicken, rat and human aggrecans have been deduced, while partial sequences have been reported for bovine aggrecan. A related proteoglycan, human versican, has also been cloned and sequenced. Both aggrecan and versican have two lectin domains, one at the amino-terminus which binds hyaluronic acid and one at the carboxyl-terminus whose physiological ligand is unknown. Both lectins have homologous counterparts in other types of proteins. Within the aggrecans the keratan sulfate domain may be variably present and also has a prominent repeat in some species. The chondroitin sulfate domain has three distinct regions which vary in their prominence in different species. The complex molecular structure of aggrecans is consistent with the concept of exon shuffling and aggrecans serve as suitable prototypes for comprehending the evolution of multi-domain proteins. 相似文献
2.
Dudhia J 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2241-2256
The primary function of articular cartilage to act as a self-renewing, low frictional material that can distribute load efficiently at joints is critically dependent upon the composition and organisation of the extracellular matrix. Aggrecan is a major component of the extracellular matrix, forming high molecular weight aggregates necessary for the hydration of cartilage and to meet its weight-bearing mechanical demands. Aggregate assembly is a highly ordered process requiring the formation of a ternary complex between aggrecan, link protein and hyaluronan. There is extensive age-associated heterogeneity in the structure and molecular stoichiometry of these components in adult human articular cartilage, resulting in diverse populations of complexes with a range of stabilities that have implications for cartilage mechanobiology and integrity. Recent findings have demonstrated that aggrecan can form ligands with other matrix proteins. These findings provide new insights into mechanisms for aggregate assembly and functional protein networks in different cartilage compartments with maturation and aging. 相似文献
3.
The effects of acetylation on the binding region of cartilage proteoglycans to hyaluronic acid 总被引:1,自引:0,他引:1
G. Quintarelli A. Vocaturo R. Zito L. Rodén 《Cellular and molecular life sciences : CMLS》1977,33(3):298-299
Summary Proteoglycans in cartilage are found as aggregates and as monomers. Evidence has been obtained indicating that hyaluronic acid, normally present in this tissue, binds together monomers into large molecular weight aggregates. In this investigation, the interacting region of the protein backbone has been studied. The results unequivocally demonstrated that the epsilon amino groups of lysine are involved in hyaluronic acid binding to proteoglycans and that their blocking by acetylation either prevents reaggregation or disaggregates the high mol. w aggregates.Supported by a grant from the Consiglio Nazionale delle Ricerche, Rome, Italy, and U. S. P. H. S., grants DE-02670 and HL 11310. 相似文献
4.
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
5.
Brooks L Heimsath EG Loring GL Brenner C 《Cellular and molecular life sciences : CMLS》2008,65(21):3458-3466
Despite the common occurrence of forkhead associated (FHA) phosphopeptide-binding domains and really interesting new gene
(RING) E3 ubiquitin ligase domains, gene products containing both an N-terminal FHA domain and C-terminal RING domain constitute
a highly distinctive intersection. Characterized FHA-RING ligases include the two vertebrate proteins, Checkpoint with FHA
and RING (Chfr) and RING finger 8 (Rnf8), as well as three fungal proteins, Defective in mitosis (Dma1), Chf1 and Chf2. These
FHA-RING ligases play roles in negative regulation of the cell division cycle, apparently by coupling protein phosphorylation
events to specific ubiquitylation of target proteins. Here, the available data on upstream and downstream regulation of and
by FHA-RING ligases are reviewed.
Received 24 April 2008; received after revision 18 June 2008; accepted 20 June 2008 相似文献
6.
J. J. Nietfeld 《Cellular and molecular life sciences : CMLS》1993,49(5):456-469
Cytokines play an important regulatory role in the metabolism of proteoglycans. Proteoglycans are found in plasma membranes, but predominantly in the extra-cellular matrix. In the latter they are quantitatively and qualitatively essential components. Especially in a tissue like cartilage without any blood vessels, the cells are dependent on cytokines for the communication among themselves in the extra-cellular matrix and also for communication with the outside world. Various cytokines have been found to be able to penetrate the extra-cellular matrix and inhibit, respectively stimulate the proteoglycan synthesis. Also, the degradation of proteoglycans can be stimulated, respectively inhibited by several cytokines. In addition, some cytokines have been found which regulate the effects of the other cytokines. With respect to proteoglycan metabolism a complex cytokine network is emerging.Furthermore it is becoming increasingly clear that proteoglycans are connected to the cytokine network by their own bioactive functions. First, they possibly possess cytokine activities themselves. Second, they can function as receptors, protectors, inactivators and storage ligands for cytokines. So the proteoglycans are clearly involved in the feedback signalling from the extra-cellular matrix to the cells that are synthesizing this extra-cellular matrix. Together with agonistic or antagonistic cytokines they are involved in the regulation of proteoglycan turnover during balanced or unbalanced metabolism in normal, respectively pathological situations. 相似文献
7.
Xin Zhu Yinwen Liang Feng Gao Junmin Pan 《Cellular and molecular life sciences : CMLS》2017,74(18):3425-3437
Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT-B complex and is also associated with cytoplasmic microtubules (MTs). Loss of IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled-coil (CC) domain binds IFT20. However, the precise function of these domains in vivo is not well understood. We showed that in Chlamydomonas, loss of IFT54 completely blocks ciliogenesis but does not affect spindle formation and proper cell cycle progression, even though IFT54 interacts with mitotic MTs. Interestingly, IFT54 lacking the CH domain allows proper flagellar assembly. The CH domain is required for the association of IFT54 with the axoneme but not with mitotic MTs, and also regulates the flagellar import of IFT54 but not IFT81 and IFT46. The C-terminal CC domain is essential for IFT54 to bind IFT20, and for its recruitment to the basal body and incorporation into IFT complexes. Complete loss of IFT54 or the CC domain destabilizes IFT20. ift54 mutant cells expressing the CC domain alone rescue the stability of IFT20 and form stunted flagella with accumulation of both IFT-A component IFT43 and IFT-B component IFT46, indicating that IFT54 also functions in IFT turn-around at the flagellar tip. 相似文献
8.
Proteoglycans of basement membranes 总被引:11,自引:0,他引:11
R. Timpl 《Cellular and molecular life sciences : CMLS》1993,49(5):417-428
Proteoglycans carrying either heparan sulfate and/or chondroitin sulfate side chains are typical constituents of basement membranes. The most prominent proteoglycan (perlecan) consists of a 400–500 kDa core protein and three heparan sulfate chains. Electron microscopy and cDNA sequencing show a complex and elongated domain structure for the core protein which in part is homologous to that of the laminin A chain. This structure may be varied by alternative splicing and proteolysis. Integration into basement membranes probably occurs by heparan sulfate binding to laminin and collagen IV, core protein binding to nidogen and by limited self assembly. The proteoglycan is in addition a cell-adhesive protein which is recognized by 1 integrins. Several more proteoglycans with smaller core proteins (10–160 kDa) apparently exist in basement membranes but are less well characterized. Biological functions include control of filtration through basement membranes and binding of growth factors and protease inhibitors. 相似文献
9.
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
10.
N. S. Fedarko 《Cellular and molecular life sciences : CMLS》1993,49(5):369-383
Purification of a protein typically involves development of a quantitative assay to track protein integrity (e.g. enzyme activity) during subsequent isolation steps. The generalized procedure involves choosing the source of the protein, defining extraction conditions, developing bulk purification methods followed by refined, more selective methods. The purification of proteoglycans is often complicated by a) limited source quantities, b) necessity of chaotropic solvents for efficient extraction, c) their large molecular size and d) lack of defined functions to enable purity (i.e. activity, conformation) to be assessed. Because the usual goal of proteoglycan purification is physical characterization (intact molecular weight, core protein and glycosaminoglycan class and size), the problems of a suitable assay and/or native conformation are avoided. The assay for tracking proteoglycan isolation typically utilizes uronic acid content or radiolabel incorporation as a marker. Once extracted from their cellular/extracellular environment, proteoglycans can be isolated by density gradient centrifugation and/or column chromatography techniques. Recent advances in the composition of chromatographic supports have enabled the application of ion-exchange, gel permeation, hydrophobic interaction and affinity chromatography resins using efficient high-pressure liquid chromatography to proteoglycan purification. 相似文献
11.
Diego-García E Abdel-Mottaleb Y Schwartz EF de la Vega RC Tytgat J Possani LD 《Cellular and molecular life sciences : CMLS》2008,65(1):187-200
Among the scorpion venom components whose function are poorly known or even show contrasting pharmacological results are those
called “orphan peptides”. The most widely distributed are named β-KTx or scorpine-like peptides. They contain three disulfide
bridges with two recognizable domains: a freely moving N-terminal amino acid sequence and a tightly folded C-terminal region
with a cysteine-stabilized α/β (CS-αβ) motif. Four such peptides and three cloned genes are reported here. They were assayed
for their cytolytic, antimicrobial and K
+ channel-blocking activities. Two main characteristics were found: the existence of an unusual structural and functional diversity,
whereby the full-length peptide can lyse cells or kill microorganisms, and a C-terminal domain containing the CS-αβ motif
that can block K
+ channels. Furthermore, sequence analyses and phylogenetic reconstructions are used to discuss the evolution of this type
of peptide and to highlight the versatility of the CS-αβ structures.
Received 13 August 2007; received after revision 30 October 2007; accepted 2 November 2007 相似文献
12.
Summary The C-terminal amino acid sequences of human and of porcine antithrombin III have been determined as Gly-Arg-Val-Ala-Asn-Pro-Cys-Val-Lys and Gly-Arg-Val-Ala-Asn-Pro-Cys, respectively. These sequences are highly homologous with the C-terminal sequence of human -1-proteinase inhibitor. 相似文献
13.
Stirnimann CU Grütter MG Glockshuber R Capitani G 《Cellular and molecular life sciences : CMLS》2006,63(14):1642-1648
DsbD is a redox-active protein of the inner Escherichia coli membrane possessing an N-terminal (nDsbD) and a C-terminal (cDsbD) periplasmic domain. nDsbD interacts with four different
redox proteins involved in the periplasmic disulfide isomerization and in the cytochrome c maturation systems. We review here the studies that led to the structural characterization of all soluble DsbD domains involved
and, most importantly, of trapped disulfide intermediate complexes of nDsbD with three of its four redox partners. These results
revealed the structural features enabling nDsbD, a ‘redox hub’ with an immunoglobulin-like fold, to interact efficiently with
its different thioredoxin-like partners.
Received 3 February 2006; received after revision 1 March 2006; accepted 5 April 2006 相似文献
14.
Christian M. Udell Thanashan Rajakulendran Frank Sicheri Marc Therrien 《Cellular and molecular life sciences : CMLS》2011,68(4):553-565
The RAF family of kinases are key components acting downstream of receptor tyrosine kinases and cells employ several distinct
mechanisms to strictly control their activity. RAF transitions from an inactive state, where the N-terminal regulatory region
binds intramolecularly to the C-terminal kinase domain, to an open state capable of executing the phosphoryl transfer reaction.
This transition involves changes both within and between the protein domains in RAF. Many different proteins regulate the
transition between inactive and active states of RAF, including RAS and KSR, which are arguably the two most prominent regulators
of RAF function. Recent developments have added several new twists to our understanding of RAF regulation. Among others, dimerization
of the RAF kinase domain is emerging as a crucial step in the RAF activation process. The multitude of regulatory protein–protein
interactions involving RAF remains a largely untapped area for therapeutic applications. 相似文献
15.
Hyaluronan synthesis and degradation in cartilage and bone 总被引:1,自引:0,他引:1
Bastow ER Byers S Golub SB Clarkin CE Pitsillides AA Fosang AJ 《Cellular and molecular life sciences : CMLS》2008,65(3):395-413
Hyaluronan (HA) is a large but simple glycosaminoglycan composed of repeating D-glucuronic acid, β1–3 linked to N-acetyl-D-glucosamine β1–4, found in body fluids and tissues, in both intra- and extracellular compartments. Despite its structural
simplicity, HA has diverse functions in skeletal biology. In development, HA-rich matrices facilitate migration and condensation
of mesenchymal cells, and HA participates in joint cavity formation and longitudinal bone growth. In adult cartilage, HA binding
to aggrecan immobilises aggrecan, retaining it at the high concentrations required for compressive resilience. HA also appears
to regulate bone remodelling by controlling osteoclast, osteoblast and osteocyte behaviour. The functions of HA depend on
its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases,
and interactions with HA-binding proteins. HA synthesis and degradation are closely regulated in skeletal tissues and aberrant
synthetic or degradative activity causes disease. The role and regulation of HA synthesis and degradation in cartilage, bone
and skeletal development is discussed.
Received 5 August 2007; received after revision 19 September 2007; accepted 20 September 2007 相似文献
16.
Panizzi P Friedrich R Fuentes-Prior P Bode W Bock PE 《Cellular and molecular life sciences : CMLS》2004,61(22):2793-2798
Staphylocoagulase (SC) secreted by Staphylococcus aureus is a potent non-proteolytic activator of the blood coagulation zymogen prothrombin and the prototype of a newly established
zymogen
activator and
adhesion
protein (ZAAP) family. The conformationally activated SC·prothrombin complex specifically cleaves fibrinogen to fibrin, which propagates the growth of bacteria-fibrin-platelet vegetations in acute bacterial endocarditis. Our recent 2.2 Å X-ray crystal structures of an active SC fragment [SC(1-325)] bound to the prothrombin zymogen catalytic domain, prethrombin 2, demonstrated that SC(1-325) represents a new type of non-proteolytic activator with a unique fold. The observed insertion of the SC(1-325) N-terminus into the Ile 16 cleft of prethrombin 2, which triggers the activating conformational change, provided the first unambiguous structural evidence for the molecular sexuality mechanism of non-proteolytic zymogen activation. Based on the SC(1-325) fold, a new family of bifunctional zymogen activator and adhesion proteins was identified that possess N-terminal domains homologous to SC(1-325) and C-terminal domains that mediate adhesion to plasma or extracellular matrix proteins. Further investigation of the ZAAP family may lead to new insights into the mechanisms of bacterial factors that hijack zymogens of the human blood coagulation and fibrinolytic systems to promote and disseminate endocarditis and other infectious diseases.Received 30 June 2004; received after revision 28 July 2004; accepted 4 August 2004 相似文献
17.
-Amylases are present in all kingdoms of the living world. Despite strong conservation of the tertiary structure, only a few amino acids are conserved in interkingdom comparisons. Animal -amylases are characterized by several typical motifs and biochemical properties. A few cases of such -amylases have been previously reported in some eubacterial species. We screened the bacterial genomes available in the sequence databases for new occurrences of animal-like -amylases. Three novel cases were found, which belong to unrelated bacterial phyla: Chloroflexus aurantiacus, Microbulbifer degradans, and Thermobifida fusca. All the animal-like -amylases in Bacteria probably result from repeated horizontal gene transfer from animals. The M. degradans genome also contains bacterial-type and plant-type -amylases in addition to the animal-type one. Thus, this species exhibits -amylases of animal, plant, and bacterial origins. Moreover, the similarities in the extra C-terminal domains (different from both the -amylase domain C and the starch-binding domain), when present, also suggest interkingdom as well as intragenomic shuffling.Received 17 October 2003; accepted 6 November 2003 相似文献
18.
Lecticans: organizers of the brain extracellular matrix 总被引:19,自引:0,他引:19
Yamaguchi Y 《Cellular and molecular life sciences : CMLS》2000,57(2):276-289
Lecticans are a family of chondroitin sulfate proteoglycans, encompassing aggrecan, versican, neurocan and brevican. These
proteoglycans are characterized by the presence of ahyaluronan-binding domain and a C-type lectin domain in their core proteins.
Through these domains, lecticans interact with carbohydrate and protein ligands in the extracellular matrix and act as linkers
of these extracellular matrix molecules. In adult brain, lecticans are thought to interact with hyaluronan and tenascin-R
to form a ternary complex. We propose that the hyaluronan-lectican-tenascin-R complex constitutes the core assembly of the
adult brain extracellular matrix, which is found mainly in pericellular spaces of neurons as ‘perineuronal nets’.
Received 27 September 1999; accepted 26 October 1999 相似文献
19.
Summary Bovine ear cartilage contains more hyaluronic acid than do hyaline cartilages of the same animal. Most of it is in the elastin-rich residue not extractable by 4 M guanidinium chloride where it is associated with chondroitin sulphate in low relative concentration and of lower molecular weight than in non-elastic cartilage residue.G. C. G. is grateful to the Medical Research Council for a research studentship. 相似文献
20.
Engen JR Wales TE Hochrein JM Meyn MA Banu Ozkan S Bahar I Smithgall TE 《Cellular and molecular life sciences : CMLS》2008,65(19):3058-3073
Src-family kinases are modular signaling proteins involved in a diverse array of cellular processes. All members of the Src
family share the same domain organization, with modular SH3, SH2 and kinase domains followed by a C-terminal negative regulatory
tail. X-ray crystallographic analyses of several Src family members have revealed critical roles for the SH3 and SH2 domains
in the down-regulation of the kinase domain. This review focuses on biological, biophysical, and computational studies that
reveal conformationally distinct active states within this unique kinase family.
Received 10 March 2008; received after revision 17 May 2008; accepted 21 May 2008 相似文献