Prediction of Collagen Stability from Amino Acid Sequence

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

doi:10.1074/jbc.m501657200

Cited by 310 publications

(367 citation statements)

References 53 publications

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“…Hostguest peptides of the form (Gly-Pro-Hyp) 3 -Gly-X-Y-(GlyPro-Hyp) 4 have been used to clarify the relation between amino acid sequence and triple-helix stability. 30 The melting temperature (T m ) values of host-guest peptides were measured by circular dichroism spectroscopy for all 20 amino acids in the X position in Gly-X-Hyp guest triplets and for 20 amino acids in the Y position in Gly-Pro-Y triplets. Interactions between X and Y residues in a Gly-X-Y guest triplet, e.g.…”

Section: Amino Acid Sequence and Triple-helix Stabilitymentioning

confidence: 99%

“…umdnj.edu/$ccalcapp). 30 Using the Collagen Stability Calculator, the amino acid sequence of a (Gly-X-Y) n peptide is entered together with information about terminal group blocking, and the predicted T m value is given. Such calculations support peptide design, since experimental T m measurements are generally within 3-48C of the predicted value.…”

Section: Amino Acid Sequence and Triple-helix Stabilitymentioning

confidence: 99%

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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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Section: Amino Acid Sequence and Triple-helix Stabilitymentioning

confidence: 99%

Section: Amino Acid Sequence and Triple-helix Stabilitymentioning

confidence: 99%

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

et al. 2008

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“…Using data from the former set, a correlation was found between OI phenotype of COL1A1 mutations and the destabilization induced by the substitutions (20). However, using data from the Gly-X-Y set, the local stability around a mutation site, approximated as the average T m of the neighboring triplets, did not show a clear association with clinical severity (21).…”

mentioning

confidence: 93%

“…One approach has been to estimate sequencespecific effects on local stability using the melting temperature (T m ) of collagen-like peptides. T m values were determined systematically for two sets of host-guest peptides, one modeling amino acid substitutions for Gly (20) and a second measuring the relative stability of 82 different Gly-X-Y triplets (21). Using data from the former set, a correlation was found between OI phenotype of COL1A1 mutations and the destabilization induced by the substitutions (20).…”

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confidence: 99%

Predicting the Clinical Lethality of Osteogenesis Imperfecta from Collagen Glycine Mutations

et al. 2008

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Osteogenesis imperfecta (OI), or brittle bone disease, often results from missense mutation of one of the conserved glycine residues present in the repeating Gly-X-Y sequence characterizing the triplehelical region of type I collagen. A composite model was developed for predicting the clinical lethality resulting from glycine mutations in the R1 chain of type I collagen. The lethality of mutations in which bulky amino acids are substituted for glycine is predicted by their position relative to the N-terminal end of the triple helix. The effect of a Gly f Ser mutation is modeled by the relative thermostability of the Gly-X-Y triplet on the carboxy side of the triplet containing the substitution. This model also predicts the lethality of Gly f Ser and Gly f Cys mutations in the R2 chain of type I collagen. The model was validated with an independent test set of six novel Gly f Ser mutations. The hypothesis derived from the model of an asymmetric interaction between a Gly f Ser mutation and its neighboring residues was tested experimentally using collagen-like peptides. Consistent with the prediction, a significant decrease in stability, calorimetric enthalpy, and folding time was observed for a peptide with a low-stability triplet C-terminal to the mutation compared to a similar peptide with the low-stability triplet on the N-terminal side. The computational and experimental results together relate the position-specific effects of Gly f Ser mutations to the local structural stability of collagen and lend insight into the etiology of OI.Collagen is a fibrous protein that provides functional and structural integrity in the human body. Type I collagen, the major protein in bone, skin, and other tissues, is a heterotrimer comprised of two R1(I) and one R2(I) polypeptide chains, encoded by the COL1A1 and COL1A2 genes, respectively. Each chain includes 338 uninterrupted repeats of the Gly-X-Y triplet, where X and Y can be any amino acid but are most often proline and hydroxyproline (Hyp or O). 1 In the heterotrimeric protein, the Gly-X-Y repeats form the triple-helical structure that is characteristic of the collagen family. The conserved glycines in every third position are essential for the integrity of the protein since larger amino acids cannot be accommodated in the tightly packed core of the triple helix without disruption of the structure.Missense mutation of a conserved Gly in the triple-helical region of type I collagen generally leads to osteogenesis imperfecta (OI). OI, often called brittle bone disease, is characterized by bone fragility and increased susceptibility to fracture, which may be accompanied by bone deformity, decreased life span, dentinogenesis imperfecta, hearing loss, and altered scleral hue (1, 2). The disease presents in a wide array of phenotypes ranging from mild to lethal. The severity depends on the chain in which the Gly substitution occurs, the location within the chain, and the substituting amino acid (3), but it is not currently possible to predict reliably the lethality fr...

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“…The basic structure of collagen-I contains three polypeptide chains, which contain the sequence repeat Glycine-X-Y motifs [7]. A proline amino acid is frequently observed at the X position and hydroxyproline being common at the Y. Collagen-I is classified among the fibril-forming collagens, which also include collagens II, III, V, XI, XXIV, XXVII which are composed of a large continuous triple helix [8,9].…”

Section: Collagen-imentioning

confidence: 99%

Extracellular Matrix Proteins in the Anterior Pituitary Gland

Kanasaki¹

2011

TONEUROEJ

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Abstract; The importance of the extracellular matrix (ECM) has become recognised as an important component of the functioning of cells. However the roles of the ECM in the anterior pituitary gland have received little attention. The pituitary has the particular characteristics of possessing a number of endocrine cells as well as less well studied nonendocrine cells. Because each cell has specific and vital roles in the physiology being of an individual the ECM must also possess selective activities. The details of ECM behaviour have not yet been delineated in the pituitary and this review first considers general characteristics of ECM compounds and then examines the properties of peptides with regard to functioning of the cells of the pituitary. It is noted that there are variations between ECM associated with normal cells and with tumours, that there are both morphological and biochemical responses to alterations in the composition of substrate on which cells are grown, and that a development of further models of ECM will be required for continued advances in the understanding of the manner in which the pituitary behaves in normal, clinical and pathological circumstances. Overall, the observations suggest that modulation of the ECM provides opportunities for enhancing well-being of individuals.

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Prediction of Collagen Stability from Amino Acid Sequence

Cited by 310 publications

References 53 publications

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

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

Predicting the Clinical Lethality of Osteogenesis Imperfecta from Collagen Glycine Mutations

Extracellular Matrix Proteins in the Anterior Pituitary Gland

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