Collagen model peptides: Sequence dependence of triple-helix stability

Persikov, Anton V.; Ramshaw, John A. M.; Brodsky, Barbara

doi:10.1002/1097-0282(2000)55:6<436::aid-bip1019>3.0.co;2-d

Cited by 118 publications

(106 citation statements)

References 77 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…All the double triplets were synthesized in two different flanking hosts (22,23), (GPP) 5 and (GPO) 3 , which provide the minimal structure to maintain triple helix stability at 20°C (24). We identified new sequences analogous to GFOGER at conserved loci within the collagen helix that can bind integrin, and confirmed the reactivity of GLOGER and GASGER.…”

mentioning

confidence: 73%

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Siljander¹,

Hamaia²,

Peachey³

et al. 2004

Journal of Biological Chemistry

164

188

View full text Add to dashboard Cite

Only three recognition motifs, GFOGER, GLOGER, and GASGER, all present in type I collagen, have been identified to date for collagen-binding integrins, such as ␣ 2 ␤ 1 . Sequence alignment was used to investigate the occurrence of related motifs in other human fibrillar collagens, and located a conserved array of novel GER motifs within their triple helical domains. We compared the integrin binding properties of synthetic triple helical peptides containing examples of such sequences (GLSGER, GMOGER, GAOGER, and GQRGER) or the previously identified motifs. Recombinant inserted (I) domains of integrin subunits ␣ 1 , ␣ 2 , and ␣ 11 bound poorly to all motifs other than GFOGER and GLOGER. Similarly, ␣ 2 ␤ 1 -containing resting platelets adhered well only to GFOGER and GLOGER, while ADP-activated platelets, HT1080 cells and two active ␣ 2 I domain mutants (E318W, locked open) bound all motifs well, indicating that affinity modulation determines the sequence selectivity of integrins. GxO/SGER peptides inhibited platelet adhesion to collagen monomers with order of potency F > L > M > A. These results establish GFOGER as a high affinity sequence, which can interact with the ␣ 2 I domain in the absence of activation and suggest that integrin reactivity of collagens may be predicted from their GER content.Collagen, the most abundant structural protein of the vertebrate organism, currently has 27 reported family members (1). As either a mechanical support or as a bioactive surface, collagen plays a crucial role in processes as diverse as morphogenesis, wound repair, inflammation, tumor metastasis, hemostasis, and thrombosis. The tensile strength of the fibrillar collagens, types I-III, V, XI, and XXVII, is crucial to the function of connective tissues including the blood vessel wall. The non-fibrillar collagens, such as types IV and VI, provide a flexible support for endothelial and epithelial cell attachment and development. Integrins, heterodimeric adhesion molecules, form an important subgroup of receptors, which mediate interaction between collagen and cells. Four ␣-subunits, ␣ 1 , ␣ 2 , ␣ 10 , and ␣ 11 , which associate non-covalently with ␤ 1 , constitute the native collagen-binding integrin family (2).Integrin ␣ 2 ␤ 1 is a well characterized and widespread receptor for collagen, laminin, and other non-matrix ligands among nucleated cells including epithelial and endothelial cells, smooth muscle cells, fibroblasts, leukocytes, and mast cells (3, 4), mediating a wide range of cellular activities. ␣ 2 ␤ 1 is the only collagen binding integrin in platelets, and is crucial for deposition on collagens exposed in damaged arterial walls (5, 6). Accordingly, the expression levels of ␣ 2 ␤ 1 have been associated with myocardial infarction and stroke (7). Recently, knockout studies suggested that the platelet activatory collagen receptor glycoprotein VI (GPVI) is mandatory for the initiation of integrin-mediated adhesion (8), but this concept was challenged by further mouse studies (9). Moreover, in vitro studies suggest that ...

show abstract

mentioning

confidence: 73%

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Siljander¹,

Hamaia²,

Peachey³

et al. 2004

Journal of Biological Chemistry

164

188

View full text Add to dashboard Cite

show abstract

“…Previous analyses have shown that arginine is the most stabilizing residue in the Y-position of the Gly-X-Y repeat. 12 On the basis of the collagen stability algorithm (http://jupiter.umdnj.edu/ collagen_calculator/), we can calculate that the R275C mutation causes local destability of the procollagen chains (DT ¼ 1.221C). 13 However, Steplewski et al 14 did not notice any change in thermostability of the entire pro-a1(II) collagen chain containing R275C.…”

Section: Discussionmentioning

confidence: 99%

“…Cysteine residues are absent in the triple helical domain of the pro-a1(II) collagen chain. 12,15 When introduced by mutation, cysteine residues may engage in creating either intramolecular or intermolecular disulfide bonds and hence unfavorably affect the supramolecular conformation of the collagen fibrillar network. 16 Cartilage analysis in a patient with the R275C mutation has shown that the fibrillar network is abnormally organized and composed of thin appearing fibrils.…”

Section: Discussionmentioning

confidence: 99%

Czech dysplasia metatarsal type: another type II collagen disorder

Hoornaert

Mařík²,

Kozlowski

et al. 2007

Eur J Hum Genet

View full text Add to dashboard Cite

Czech dysplasia metatarsal type is an autosomal-dominant disorder characterized by an early-onset, progressive spondyloarthropathy with normal stature. Shortness of third and/or fourth toes is a frequently observed clinical feature. Similarities between individuals with this dysplasia and patients with an R275C mutation in the COL2A1 gene, prompted us to analyze the COL2A1 gene in the original families reported with Czech dysplasia. Targeted sequencing of exon 13 of the COL2A1 gene was performed, followed by sequencing of the remaining exons in case the R275C mutation was not identified. We identified the R275C substitution in two of the original patients reported with Czech dysplasia and three additional patients. All affected individuals had a similar phenotype characterized by normal height, spondyloarthropathy, short postaxial toes and absence of ocular and orofacial anomalies. The R275C mutation was excluded in a third patient reported with Czech dysplasia. However, the identification of the Y1391C mutation in this patient with disproportionate short stature made the diagnosis of spondyloperipheral dysplasia (SPD) more probable. The Y1391C mutation is located in the C-propeptide of the procollagen chain and has been reported before in a patient with the Torrance type of lethal platyspondylic skeletal dysplasia (PLSD-T). Our observation of the same Y1391C mutation in an additional unrelated patient with SPD further supports the evidence that PLSD-T and SPD represent a phenotypic continuum. The R275C mutation in the COL2A1 gene causes a specific type II collagen disorder that was recently delineated as Czech dysplasia.

show abstract

“…For example, Gly-Asp-Lys is destabilizing for the triple helix compared with Gly-Pro-Hyp. (Gly-Pro-Hyp) 3 -Gly-Asp-Lys-(Gly-Pro-Hyp) 4 -Gly-Gly had a melting temperature (T m ) value of 30.9°C, whereas (Gly-ProHyp) 3 -Gly-Pro-Hyp-(Gly-Pro-Hyp) 4 -Gly-Gly had a T m value of 47.3°C (35). In contrast, Lys-Gly-Asp offers triple-helix stability comparable with Hyp-Gly-Pro.…”

mentioning

confidence: 99%

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Lauer

Bhowmick

Tokmina‐Roszyk

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The role of charged clusters in modulating MMP hydrolysis of collagen is unknown. Results: Triple-helical peptides containing charged motifs were as good or better substrates than the parent (non-chargeclustered) peptide. Conclusion: MMP-2 and MMP-9 greatly favored the presence of charged residues. Significance: The lack of Gly-Asp-Lys clusters in native collagens may diminish potential MMP-2 and MMP-9 collagenolytic activity.

show abstract

Collagen model peptides: Sequence dependence of triple-helix stability

Cited by 118 publications

References 77 publications

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens

Czech dysplasia metatarsal type: another type II collagen disorder

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Contact Info

Product

Resources

About