Design, Structure and Applications of Collagen-Mimetic Peptides
type: CreativeWork
description: The collagen triple helix is a unique protein fold found in all domains of life where is has diverse roles from imparting structure and strength to tissue, to initiating an immune response. While many factors affecting the structure and stability of the triple helix have previously been elucidated, much remains unknown about collagen. Using collagen-mimetic peptides, it is possible to investigate the molecular structure of the triple helix, determine new pairwise interactions of amino acids, characterize disease models and also create designer collagens that will preferentially hybridize to natural collagen-rich tissue. First a selective labeling scheme is used to thoroughly characterize a well-folded triple helical region, and then to determine the degree of localized unfolding at the N- and C-termini. Though terminal fraying extends farther than previously shown, small sequence alterations at the N-terminus have a drastic influence on local stability (~15C). Next, a single register heterotrimeric mimic of the type I collagen disease Osteogenesis Imperfecta is used to investigate single point glycine mutations in the B chain, the A chain or both chains. Unlike past reports, a combination of NMR analysis and molecular modelling is used to generate structures of the mutated helices and visualize the underlying mechanisms of helix destabilization in OI. For the first time it is proven that these mutations cause compositional as well as structural disruptions. Additionally, while several hundred pairwise interactions are possible in the triple helix, to date only two interactions are wellunderstood and commonly incorporated into CMP design. To expand on the library of known interactions, the structure and stability of helices containing serine, threonine, phospho-serine and phospho-threonine were investigated. Notably, when phospho-serine is paired with lysine a new highly stabilizing (49.5 C) axial interaction is possible. Finally, the design of a collagen type II tar…
abstract: The collagen triple helix is a unique protein fold found in all domains of life where is has diverse roles from imparting structure and strength to tissue, to initiating an immune response. While many factors affecting the structure and stability of the triple helix have previously been elucidated, much remains unknown about collagen. Using collagen-mimetic peptides, it is possible to investigate the molecular structure of the triple helix, determine new pairwise interactions of amino acids, characterize disease models and also create designer collagens that will preferentially hybridize to natural collagen-rich tissue. First a selective labeling scheme is used to thoroughly characterize a well-folded triple helical region, and then to determine the degree of localized unfolding at the N- and C-termini. Though terminal fraying extends farther than previously shown, small sequence alterations at the N-terminus have a drastic influence on local stability (~15C). Next, a single register heterotrimeric mimic of the type I collagen disease Osteogenesis Imperfecta is used to investigate single point glycine mutations in the B chain, the A chain or both chains. Unlike past reports, a combination of NMR analysis and molecular modelling is used to generate structures of the mutated helices and visualize the underlying mechanisms of helix destabilization in OI. For the first time it is proven that these mutations cause compositional as well as structural disruptions. Additionally, while several hundred pairwise interactions are possible in the triple helix, to date only two interactions are wellunderstood and commonly incorporated into CMP design. To expand on the library of known interactions, the structure and stability of helices containing serine, threonine, phospho-serine and phospho-threonine were investigated. Notably, when phospho-serine is paired with lysine a new highly stabilizing (49.5 C) axial interaction is possible. Finally, the design of a collagen type II tar…
author: Acevedo-Jake, Amanda M
language: eng
keywords: collagen, protein design
date published: 2017-04-25
date modified: 2026-07-24T04:10:30Z
provider: Rice University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rice University

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1911/96078