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Glycine substitutions in collagen heterotrimers alter triple helical assembly

Glycine substitutions in collagen heterotrimers alter triple helical assembly
Glycine substitutions in collagen heterotrimers alter triple helical assembly
Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present. Here we present mutations to a composition- and register-controlled AAB helix where one of the requisite glycines in the A chain of the triple helix is changed to serine or alanine. We see a loss of compositional control when the A chain is mutated, resulting in an A′BB composition that minimizes the number of mutations included in the triple helix. However, when both A and B chains are mutated and no nonmutated peptide chains are available, the designed A′A′B′ composition is reestablished. Our work shows the ability of the mutations to influence and alter the composition and register of the collagen triple helix.
1525-7797
617-624
Clements, Katherine A.
c450795d-63da-45b6-bf68-2f76326931b9
Acevedo-Jake, Amanda M.
648b12e3-763b-4e0b-bf33-abf4f85be1ef
Walker, Douglas R.
043fc749-8794-416b-8dee-877f6285e167
Hartgerink, Jeffrey D.
37f5e1c8-1280-4133-8584-b327d6fcaaeb
Clements, Katherine A.
c450795d-63da-45b6-bf68-2f76326931b9
Acevedo-Jake, Amanda M.
648b12e3-763b-4e0b-bf33-abf4f85be1ef
Walker, Douglas R.
043fc749-8794-416b-8dee-877f6285e167
Hartgerink, Jeffrey D.
37f5e1c8-1280-4133-8584-b327d6fcaaeb

Clements, Katherine A., Acevedo-Jake, Amanda M., Walker, Douglas R. and Hartgerink, Jeffrey D. (2017) Glycine substitutions in collagen heterotrimers alter triple helical assembly. Biomacromolecules, 18 (2), 617-624. (doi:10.1021/acs.biomac.6b01808).

Record type: Article

Abstract

Osteogenesis imperfecta typically results from missense mutations in the collagen genome where the required glycine residues are replaced with another amino acid. Many models have attempted to replicate the structure of mutated collagen on the triple helix level. However, composition and register control of the triple helix is complicated and requires extreme precision, especially when these destabilizing mutations are present. Here we present mutations to a composition- and register-controlled AAB helix where one of the requisite glycines in the A chain of the triple helix is changed to serine or alanine. We see a loss of compositional control when the A chain is mutated, resulting in an A′BB composition that minimizes the number of mutations included in the triple helix. However, when both A and B chains are mutated and no nonmutated peptide chains are available, the designed A′A′B′ composition is reestablished. Our work shows the ability of the mutations to influence and alter the composition and register of the collagen triple helix.

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More information

Accepted/In Press date: 1 April 2016
e-pub ahead of print date: 18 January 2017
Published date: 13 February 2017

Identifiers

Local EPrints ID: 434654
URI: http://eprints.soton.ac.uk/id/eprint/434654
ISSN: 1525-7797
PURE UUID: bddf7fb9-65f2-4b8b-bdba-d0d67cd9b15e

Catalogue record

Date deposited: 04 Oct 2019 16:30
Last modified: 06 Oct 2020 18:33

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