Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils

Steplewski, Andrzej; Ito, Hidetoshi; Rucker, Eileen; Brittingham, Raymond; Alabyeva, Tatiana; Gandhi, Milind; Ko, Frank; Birk, David E.; Jimenez, Sergio A.; Fertala, Andrzej

doi:10.1016/j.jsb.2004.07.006

Cited by 45 publications

(64 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Crystal structures of collagen peptides show that variation in amino acid content leads to small but significant variations in the superhelix twist (9 -11). Calorimetric results suggest the presence of multiple independent folding domains along a collagen molecule (12), and the presence of regions of different stability was confirmed by recent studies on recombinant collagen constructs (13). There are multiple binding domains in collagens (14), and regions of decreased triple helix stability have been implicated in binding in some cases (15)(16)(17).…”

mentioning

confidence: 66%

Prediction of Collagen Stability from Amino Acid Sequence

Persikov¹,

Ramshaw

Brodsky³

2005

Journal of Biological Chemistry

314

344

View full text Add to dashboard Cite

An algorithm was derived to relate the amino acid sequence of a collagen triple helix to its thermal stability. This calculation is based on the triple helical stabilization propensities of individual residues and their intermolecular and intramolecular interactions, as quantitated by melting temperature values of host-guest peptides. Experimental melting temperature values of a number of triple helical peptides of varying length and sequence were successfully predicted by this algorithm. However, predicted T m values are significantly higher than experimental values when there are strings of oppositely charged residues or concentrations of like charges near the terminus. Application of the algorithm to collagen sequences highlights regions of unusually high or low stability, and these regions often correlate with biologically significant features. The prediction of stability from sequence indicates an understanding of the major forces maintaining this protein motif. The use of highly favorable KGE and KGD sequences is seen to complement the stabilizing effects of imino acids in modulating stability and may become dominant in the collagenous domains of bacterial proteins that lack hydroxyproline. The effect of single amino acid mutations in the X and Y positions can be evaluated with this algorithm. An interactive collagen stability calculator based on this algorithm is available online.The ability to predict structure and stability from amino acid sequence is an important step in the understanding of basic protein principles and the structural consequences of pathological mutations. The vast number of amino acid sequences available from DNA data contrasts with the smaller number of high resolution protein structures and the limited experimental data on protein stability. The ability to make predictions that are in good agreement with experimental data provides insight into the stabilizing interactions within proteins. In addition, there is much interest in computing the effect of single amino acid replacements on protein stability because destabilizing effects are associated with deleterious mutations that result in clinically detectable phenotypes (1-3). In contrast to globular proteins, the relation among sequence, structure, and stability is simpler and better defined for the linear collagen triple helix.The collagen triple helix motif is found widely in structural proteins of the extracellular matrix and in an increasing set of non-collagenous proteins, many of which are involved in host-defense functions (4, 5). The close packing of three supercoiled polyproline II-like polypeptide chains in the collagen triple helix generates a requirement for Gly as every third residue (6 -8). The observation of such a repeating (Gly-X-Y) n sequence pattern over a stretch of residues signifies a triple helix conformation. However, the collagen triple helix is not uniform in structure or stability. Crystal structures of collagen peptides show that variation in amino acid content leads to small but significant variations i...

show abstract

mentioning

confidence: 66%

Prediction of Collagen Stability from Amino Acid Sequence

Persikov¹,

Ramshaw

Brodsky³

2005

Journal of Biological Chemistry

314

344

View full text Add to dashboard Cite

show abstract

“…The studies on Arg789Cys collagen revealed abnormal structure, the presence of disulfide bonds, and low thermostability [Steplewski et al, 2004b]. This collagen was unable to assemble into fibrils.…”

Section: Discussionmentioning

confidence: 99%

Novel amino acid substitution in the Y‐position of collagen type II causes spondyloepimetaphyseal dysplasia congenita

Sułko

Czarny-Ratajczak

Woźniak

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We report on monozygotic twins with short stature and severe spondyloepimetaphyseal dysplasia congenita (SEMDC) from the Polish population. Phenotype of the twin girls resembles spondyloepiphyseal dysplasia congenita Spranger-Wiedemann (SEDC-SW), but shortening of the stature is more severe and the cranioface is normal. The distinctive radiographic features, in spite of similarity to SEDC-SW, indicate different spinal and, notably, severe metaphyseal involvement. Molecular analysis of the COL2A1 gene revealed an A to G transition at nucleotide þ79 of exon 41 that converted the codon for arginine at amino acid 792 to a codon for glycine (Arg792Gly). The twins were heterozygous for the mutation and neither parent had this change. The Arg792Gly substitution is located at the Y-position of Gly-X-Y triplet, and it is likely that this substitution decreased the thermal stability of the triple helix and may affect fibril growth by replacement of an arginine residue, which is important for a conformation of the triple helix.

show abstract

“…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. 8 In one patient (AK0607560), reported previously to be affected by Czech dysplasia, the R275C mutation was excluded.…”

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

Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils

Cited by 45 publications

References 44 publications

Prediction of Collagen Stability from Amino Acid Sequence

Prediction of Collagen Stability from Amino Acid Sequence

Novel amino acid substitution in the Y‐position of collagen type II causes spondyloepimetaphyseal dysplasia congenita

Czech dysplasia metatarsal type: another type II collagen disorder

Contact Info

Product

Resources

About