Document Detail


Assembly pathway of a designed alpha-helical protein fiber.
MedLine Citation:
PMID:  20409488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interest in the design of peptide-based fibrous materials is growing because it opens possibilities to explore fundamental aspects of peptide self-assembly and to exploit the resulting structures--for example, as scaffolds for tissue engineering. Here we investigate the assembly pathway of self-assembling fibers, a rationally designed alpha-helical coiled-coil system comprising two peptides that assemble on mixing. The dimensions spanned by the peptides and final structures (nanometers to micrometers), and the timescale over which folding and assembly occur (seconds to hours), necessitate a multi-technique approach employing spectroscopy, analytical ultracentrifugation, electron and light microscopy, and protein design to produce a physical model. We show that fibers form via a nucleation and growth mechanism. The two peptides combine rapidly (in less than seconds) to form sticky ended, partly helical heterodimers. A lag phase follows, on the order of tens of minutes, and is concentration-dependent. The critical nucleus comprises six to eight partially folded dimers. Growth is then linear in dimers, and subsequent fiber growth occurs in hours through both elongation and thickening. At later times (several hours), fibers grow predominantly through elongation. This kinetic, biomolecular description of the folding-and-assembly process allows the self-assembling fiber system to be manipulated and controlled, which we demonstrate through seeding experiments to obtain different distributions of fiber lengths. This study and the resulting mechanism we propose provide a potential route to achieving temporal control of functional fibers with future applications in biotechnology and nanoscale science and technology.
Authors:
Elizabeth H C Bromley; Kevin J Channon; Patrick J S King; Zahra N Mahmoud; Eleanor F Banwell; Michael F Butler; Matthew P Crump; Timothy R Dafforn; Matthew R Hicks; Jonathan D Hirst; Alison Rodger; Derek N Woolfson
Related Documents :
11911778 - Fibrillin: from microfibril assembly to biomechanical function.
20158218 - Self-assembling multidomain peptide hydrogels: designed susceptibility to enzymatic cle...
23934148 - Bidirectional processing of pri-mirnas with branched terminal loops by arabidopsis dice...
17270198 - Structural control of peptide-coated gold nanoparticle assemblies by the conformational...
1530638 - Interaction mode of n-dodecylphosphorylcholine, a substrate analogue, with bovine pancr...
234458 - Circular dichroism of c3a anaphylatoxin. effects of ph, heat, guanidinium chloride, and...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biophysical journal     Volume:  98     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-08     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1668-76     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Circular Dichroism
Models, Molecular
Mutagenesis / genetics
Peptides / chemistry,  metabolism
Proline / genetics
Protein Folding
Protein Structure, Secondary*
Proteins / chemistry*,  metabolism,  ultrastructure
Grant Support
ID/Acronym/Agency:
E022359//Biotechnology and Biological Sciences Research Council; MC_U117533887//Medical Research Council
Chemical
Reg. No./Substance:
0/Peptides; 0/Proteins; 9DLQ4CIU6V/Proline
Comments/Corrections

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


Previous Document:  Probing a structural model of the nuclear pore complex channel through molecular dynamics.
Next Document:  Intrinsic determinants of neurotoxic aggregate formation by the amyloid beta peptide.