The Collagen Family: Structure, Assembly, and Organization in the Extracellular Matrix

Kielty, Cay M.; Grant, Michael E.

doi:10.1002/0471221929.ch2

Cited by 260 publications

(318 citation statements)

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“…These exons constitute the carboxypropeptide of the procollagen a1(II)-chain, which is necessary for chain association and initiation of the triple helix formation. 24 Consequently, the resulting truncated protein will most likely be lost and not incorporated into the collagen trimer. In the isoform A2, exon 7 was deleted but intron 5 retained, the latter containing an in-frame stop codon.…”

Section: Resultsmentioning

confidence: 99%

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Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

et al. 2010

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Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (Po0.01). Overall, 20 of 23 sporadic patients with a COL2A1 mutation had either a cleft palate or retinal detachment with vitreous anomalies. The presence of vitreous anomalies, retinal tears or detachments, cleft palate and a positive family history were shown to be good indicators for a COL2A1 defect. In conclusion, we confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene as 490% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome.

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Section: Resultsmentioning

confidence: 99%

“…15 The probe set for COL2A1 (SALSA MLPA kit P214) covering exons 1,4,6,8,10,16,17,19,20,24,27,29,31,35,39,43,46, 49, 51 and 54 was used.…”

Section: Mlpa Analysismentioning

confidence: 99%

Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

et al. 2010

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“…31,32 The most abundant are the fibril forming collagens (Types I, II, III, V, XI) and these molecules have Gly as every 3rd residue throughout their $1000 residue triple-helix domain. Although the presence of Gly as every 3rd residue is a defining feature necessary to have a classic triple helix without distortion, it is now clear that the (Gly-X-Y) n repeat is perfect only in fibril forming collagens.…”

Section: Natural Interruptions In the Gly-x-y Repeating Pattern In Nomentioning

confidence: 99%

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

et al. 2008

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Peptides have been an integral part of the collagen triple‐helix structure story, and have continued to serve as useful models for biophysical studies and for establishing biologically important sequence‐structure‐function relationships. High resolution structures of triple‐helical peptides have confirmed the basic Ramachandran triple‐helix model and provided new insights into the hydration, hydrogen bonding, and sequence dependent helical parameters in collagen. The dependence of collagen triple‐helix stability on the residues in its (Gly‐X‐Y)n repeating sequence has been investigated by measuring melting temperatures of host‐guest peptides and an on‐line collagen stability calculator is now available. Although the presence of Gly as every third residue is essential for an undistorted structure, interruptions in the repeating (Gly‐X‐Y)n amino acid sequence pattern are found in the triple‐helical domains of all nonfibrillar collagens, and are likely to play a role in collagen binding and degradation. Peptide models indicate that small interruptions can be incorporated into a rod‐like triple‐helix with a highly localized effect, which perturbs hydrogen bonds and places the standard triple‐helices on both ends out of register. In contrast to natural interruptions, missense mutations which replace one Gly in a triple‐helix domain by a larger residue have pathological consequences, and studies on peptides containing such Gly substitutions clarify their effect on conformation, stability, and folding. Recent studies suggest peptides may also be useful in defining the basic principles of collagen self‐association to the supramolecular structures found in tissues. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 345–353, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…Collagen is the major constituent of the extracellular matrix and the most abundant protein in animals [Kielty and Grant, 2002]. The fibril-forming collagens provide structural integrity to bone, skin, cartilage, blood vessels, and other organs.…”

Section: Introductionmentioning

confidence: 99%

COLdb, a database linking genetic data to molecular function in fibrillar collagens

Bodian

Klein

2009

Hum. Mutat.

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Fibrillar collagens are ubiquitous proteins essential for the structural integrity of bones, skin, blood vessels, and other tissues. Mutations in collagen genes result in disorders including osteogenesis imperfecta, chondrodysplasias, and Ehlers-Danlos syndromes, but the molecular basis for the heterogeneity of clinical phenotypes is not well understood. A more complete understanding of the relationship between sequence and phenotype requires synthesis of multiple facets of collagen structure and function. To facilitate such an analysis, we developed COLdb, a freely available database integrating collagen biological and physicochemical properties with known variants. A Web-based, interactive, graphical user interface displays the data as annotations on the collagen protein sequences. Collagen gene-level data are provided as custom tracks for display in the UCSC genome browser. COLdb currently includes 35,582 data points spanning collagen types I, II, and III, and, importantly, users can add their own data to the display. The database is the first comprehensive integration of disparate functional information on the three major fibrillar collagens, and the first electronic collection of mutations in the COL2A1 gene. Hum Mutat 30,[946][947][948][949][950][951]

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The Collagen Family: Structure, Assembly, and Organization in the Extracellular Matrix

Cited by 260 publications

References 0 publications

Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

COLdb, a database linking genetic data to molecular function in fibrillar collagens

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