Conformational stability of type I collagen triple helix: Evidence for temporary and local relaxation of the protein conformation using a proteolytic probe

1983 ◽  
Vol 223 (2) ◽  
pp. 562-571 ◽  
Author(s):  
Lasse Ryhänen ◽  
Edward J. Zaragoza ◽  
Jouni Uitto
Keyword(s):  
Protein Conformation ◽  
Triple Helix ◽  
Type I Collagen ◽  
Conformational Stability ◽  
Type I ◽  
Collagen Triple Helix ◽  
Local Relaxation

scholarly journals Structural Heterogeneity of Type I Collagen Triple Helix and Its Role in Osteogenesis Imperfecta

2007 ◽  
Vol 283 (8) ◽  
pp. 4787-4798 ◽  
Author(s):  
Elena Makareeva ◽  
Edward L. Mertz ◽  
Natalia V. Kuznetsova ◽  
Mary B. Sutter ◽  
Angela M. DeRidder ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Structural Heterogeneity ◽  
Type I ◽  
Collagen Triple Helix

scholarly journals Characterization of three osteogenesis imperfecta collagen α 1(I) glycine to serine mutations demonstrating a position-dependent gradient of phenotypic severity

1992 ◽  
Vol 288 (1) ◽  
pp. 131-135 ◽  
Author(s):  
J F Bateman ◽  
I Moeller ◽  
M Hannagan ◽  
D Chan ◽  
W G Cole
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Type I ◽  
Disruptive Effect ◽  
Collagen Triple Helix ◽  
C Terminus ◽  
Glycine Substitution ◽  
C And N

Type I collagen alpha 1(I) glycine to serine substitutions, resulting from G-to-A mutations, were defined in three cases of osteogenesis imperfecta (OI). The Gly substitutions displayed a gradient of phenotypic severity according to the location of the mutation in the collagen triple helix. The most C-terminal of these, Gly565 to Ser, led to the lethal perinatal (type II) form of OI, whereas the more N-terminal mutations, Gly415 and Gly352 to Ser, led to severe OI (type III/IV) and moderate OI (type IVB) respectively. These data support the notion that glycine substitutions towards the C-terminus of the alpha 1(I) or alpha 2(I) chains will be more clinically severe than those towards the N-terminus. This results from the more disruptive effect of the mutations at the C-terminus on helix initiation and C- and N-terminal helix directional propagation. This generalization must be modified by considering the nature of the glycine substitution and the surrounding amino acid sequence, since the helix is composed of subdomains of differing stability which will affect the ability of helix re-nucleation and propagation.

scholarly journals Re-evaluation of lysyl hydroxylation in the collagen triple helix: lysyl hydroxylase 1 and prolyl 3-hydroxylase 3 have site-differential and collagen type-dependent roles in lysine hydroxylation

2019 ◽  
Author(s):  
Yoshihiro Ishikawa ◽  
Yuki Taga ◽  
Keith Zientek ◽  
Nobuyo Mizuno ◽  
Antti M. Salo ◽  
...  
Keyword(s):  
Triple Helix ◽  
Type I Collagen ◽  
Type I ◽  
Post Translational Modifications ◽  
Type V Collagen ◽  
Collagen Triple Helix ◽  
Type V ◽  
Lysyl Hydroxylase 1 ◽  
Lysine Hydroxylation ◽  
Molecular Ensemble

AbstractCollagen is the most abundant protein in humans and is heavily post-translationally modified. Its biosynthesis is very complex and requires three different types of hydroxylation (two for proline and one for lysine) that are generated in the rough endoplasmic reticulum (rER). These processes involve many enzymes and chaperones which were collectively termed the molecular ensemble for collagen biosynthesis. However, the function of some of the proteins in this molecular ensemble is controversial. While prolyl 3-hydroxylase 1 and 2 (P3H1, P3H2) are bona fide collagen prolyl 3-hydroxylases, the function of prolyl 3-hydroxylase 3 (P3H3) is less clear. A recent study of P3H3 null mice demonstrated that this enzyme had no activity as prolyl 3-hydroxylase but may instead act as a chaperone for lysyl hydroxylase 1 (LH1). LH1 is required to generate hydroxylysine for crosslinking within collagen triple helical sequences. If P3H3 is a LH1 chaperone that is critical for LH1 activity, P3H3 and LH1 null mice should have similar deficiency in lysyl hydroxylation. To test this hypothesis, we compared lysyl hydroxylation in type I and V collagen from P3H3 and LH1 null mice. Our results indicate LH1 plays a global role for lysyl hydroxylation in triple helical domain of type I collagen while P3H3 is indeed involved in lysyl hydroxylation particularly at crosslink formation sites but is not required for all lysyl hydroxylation sites in type I collagen triple helix. Furthermore, although type V collagen from LH1 null mice surprisingly contained as much hydroxylysine as type V collagen from wild type, the amount of hydroxylysine in type V collagen was clearly suppressed in P3H3 null mice. In summary, our study suggests that P3H3 and LH1 likely have two distinct mechanisms to distinguish crosslink formation sites from other sites in type I collagen and to recognize different collagen types in the rER.Author summaryCollagen is one of the most heavily post-translationally modified proteins in the human body and its post-translational modifications provide biological functions to collagen molecules. In collagen post-translational modifications, crosslink formation on a collagen triple helix adds important biomechanical properties to the collagen fibrils and is mediated by hydroxylation of very specific lysine residues. LH1 and P3H3 show the similar role in lysine hydroxylation for specific residues at crosslink formation sites of type I collagen. Conversely, they have very distinct rules in lysine hydroxylation at other residues in type I collagen triple helix. Furthermore, they demonstrate preferential recognition and modification of different collagen types. Our findings provide a better understanding of the individual functions of LH1 and P3H3 in the rER and also offer new directions for the mechanism of lysyl hydroxylation followed by crosslink formation in different tissues and collagens.

The effect of theL-azetidine-2-carboxylic acid residue on protein conformation. IV. Local substitutions in the collagen triple helix

Biopolymers ◽  
1994 ◽  
Vol 34 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Adriana Zagari ◽  
Kathleen A. Palmer ◽  
Kenneth D. Gibson ◽  
George Némethy ◽  
Harold A. Scheraga
Keyword(s):  
Carboxylic Acid ◽  
Protein Conformation ◽  
Triple Helix ◽  
Collagen Triple Helix

Influence of Mechanical Load on the Degradation of Corneal Collagen

2008 ◽  
Author(s):  
Ramin Zareian ◽  
Kelli P. Church ◽  
Jeffrey W. Ruberti
Keyword(s):  
Self Assembly ◽  
Type I Collagen ◽  
Mechanical Load ◽  
Structural Performance ◽  
Type I ◽  
Connective Tissues ◽  
Bacterial Collagenase ◽  
Collagen Triple Helix ◽  
Different Types ◽  
Corneal Collagen

Collagen is one of the most important structural proteins in vertebrate animals. Over 25 different types of collagen have been identified, but type I collagen is the most abundant fibril forming collagen and contributes to the structural performance numerous connective tissues including ligaments, tendons and cornea [1]. In addition to collagen self-assembly, collagen degradation is an important step in the development, remodeling, homeostasis and pathology of load-bearing ECM. Matrix Metalloproteinase (MMP) types I and VIII, bacterial collagenase and cathepsin are the best known enzymes capable of directly degrading the collagen triple helix [2, 3]. Several researchers have hypothesized that straining collagen fibrils makes them less susceptible to enzymatic degradation [4, 5]. This concept, which we refer to as “strain-stabilization” has important implications for our understanding of collagen as an engineering material.

scholarly journals The Characteristics of Intrinsic Fluorescence of Type I Collagen Influenced by Collagenase I

2018 ◽  
Vol 8 (10) ◽  
pp. 1947 ◽  
Author(s):  
Yiming Shen ◽  
Deyi Zhu ◽  
Wenhui Lu ◽  
Bing Liu ◽  
Yanchun Li ◽  
...  
Keyword(s):  
Fluorescence Intensity ◽  
Self Assembly ◽  
Triple Helix ◽  
Type I Collagen ◽  
Intrinsic Fluorescence ◽  
Type I ◽  
Food And Agriculture ◽  
Mechanism Research ◽  
Helix Structure ◽  
Assembly Behavior

The triple helix structure of collagen can be degraded by collagenase. In this study, we explored how the intrinsic fluorescence of type I collagen was influenced by collagenase I. We found that tyrosine was the main factor that could successfully excite the collagen fluorescence. Initially, self-assembly behavior of collagen resulted in a large amount of tyrosine wrapped with collagen, which decreased the fluorescence intensity of type I collagen. After collagenase cleavage, some wrapped-tyrosine could be exposed and thereby the intrinsic fluorescence intensity of collagen increased. By observation and analysis, the influence of collagenase to intrinsic fluorescence of collagen was investigated and elaborated. Furthermore, collagenase cleavage to the special triple helix structure of collagen would result in a slight improvement of collagen thermostability, which was explained by the increasing amount of terminal peptides. These results are helpful and effective for reaction mechanism research related to collagen, which can be observed by fluorescent technology. Meantime, the reaction behaviors of both collagenase and collagenolytic proteases can also be analyzed by fluorescent technology. In conclusion, this research provides a foundation for the further investigation of collagen reactions in different areas, such as medicine, nutrition, food and agriculture.

scholarly journals Human cathepsin K cleaves native type I and II collagens at the N-terminal end of the triple helix

1998 ◽  
Vol 331 (3) ◽  
pp. 727-732 ◽  
Author(s):  
Wa'el KAFIENAH ◽  
Dieter BRÖMME ◽  
David J. BUTTLE ◽  
Lisa J. CROUCHER ◽  
Anthony P. HOLLANDER
Keyword(s):  
Cleavage Site ◽  
Triple Helix ◽  
Type I Collagen ◽  
Cathepsin K ◽  
Type Ii Collagen ◽  
Collagenolytic Activity ◽  
Type I ◽  
Type Ii ◽  
Helical Domain ◽  
N Terminus

Cathepsin K (EC 3.4.22.38) is a recently described enzyme that has been shown to cleave type I collagen in its triple helix. The aim of this study was to determine if it also cleaves type II collagen in the triple helix and to identify the helical cleavage site(s) in types I and II collagens. Soluble human and bovine type II collagen, and rat type I collagen, were incubated with cathepsin K before the reaction was stopped with trans-epoxysuccinyl-l-leucylamido-(4-guanidino)butane (E-64). Analysis by SDS/PAGE of the collagen digests showed that optimal activity of cathepsin K against native type II collagen was between pH 5.0 and 5.5 and against denatured collagen between pH 4.0 and 7.0. The enzyme cleaved telopeptides as well as the α1(II) chains, generating multiple fragments in the range 90–120 kDa. The collagenolytic activity was not due to a contaminating metalloenzyme or serine proteinase as it was not inhibited by 1,10-phenanthroline, EDTA or 3,4-dichloroisocoumarin. Western blotting with anti-peptide antibodies to different regions of the α1(II) chain suggested that cathepsin K cleaved native α1(II) chains in the N-terminal region of the helical domain rather than at the well-defined collagenase cleavage site. This was confirmed by N-terminal sequencing of one of the fragments, revealing cleavage at a Gly-Lys bond, 58 residues from the N-terminus of the helical domain. By using a similar approach, cathepsin K was found to cleave native type I collagen close to the N-terminus of its triple helix. These results indicate that cathepsin K could have a role in the turnover of type II collagen, as well as type I collagen.

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