Document Detail


Surprisingly high stability of collagen ABC heterotrimer: evaluation of side chain charge pairs.
MedLine Citation:
PMID:  17988128     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Type I collagen is a major component of skin, tendon, and ligament and forms more than 90% of bone mass. It is an AAB heterotrimer assembled from two identical alpha1 and one alpha2 chains. However, the majority of studies on the effects of amino acid substitution on triple helix stability have been performed on collagen homotrimeric helices. In a homotrimer, it is impossible to determine whether the contribution to stability is from the polyproline II helix propensity of the amino acids or from interhelix amino acid interactions. The presence of amino acids in all three chains further exaggerates their contribution. In contrast, in a heterotrimer, the individual chains may be tailored in order to have the substitution in one, two, or all three chains. Therefore, a heterotrimer can divulge specific information about any interaction based upon the substitutions in individual chains. In this paper, we evaluate the contribution of electrostatic interactions between side chain charge pairs on the stability of heterotrimers. We synthesize and analyze the stability of four AAB and four ABC heterotrimers including a surprisingly stable ABC heterotrimer composed of (DOG)10, (PKG)10, and (POG)10 chains (O = hydroxyproline). This heterotrimer has a stability comparable to that of a (POG)10 homotrimer even though D and K occur 20 times in the heterotrimeric helix and have been previously shown to significantly destabilize the triple helix compared to the P and O imino acids. These results show that the stability of heterotrimers cannot be directly determined from the analysis of charge pairs in homotrimers. Because collagen heterotrimers can be designed to have substitution in one, two, or three chains, it gives us the ability to decode cross-strand interactions in collagen in a similar fashion to alpha-helical coiled-coil interactions and DNA duplex hydrogen bonding.
Authors:
Varun Gauba; Jeffrey D Hartgerink
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-11-08
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  129     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-28     Completed Date:  2008-01-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15034-41     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Rice University, 6100 Main Street, Mail Stop 60, Houston, Texas 77005, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Circular Dichroism
Collagen / chemistry*,  metabolism*
Models, Molecular
Peptides / chemistry
Protein Binding
Protein Denaturation
Protein Structure, Quaternary
Protein Structure, Secondary
Static Electricity
Temperature
Chemical
Reg. No./Substance:
0/Peptides; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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