edoc

Continuous molecular evolution of protein-domain structures by single amino acid changes

Meier, S. and Jensen, P. R. and David, C. N. and Chapman, J. and Holstein, T. W. and Grzesiek, S. and Ozbek, S.. (2007) Continuous molecular evolution of protein-domain structures by single amino acid changes. Current Biology, 17 (2). pp. 173-178.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5258771

Downloads: Statistics Overview

Abstract

Protein structures cluster into families of folds that can result from extremely different amino acid sequences [1]. Because the enormous amount of genetic information generates a limited number of protein folds [2], a particular domain structure often assumes numerous functions. How new protein structures and new functions evolve under these limitations remains elusive. Molecular evolution may be driven by the ability of biomacromolecules to adopt multiple conformations as a bridge between different folds [3-6]. This could allow proteins to explore new structures and new tasks while part of the structural ensemble retains the initial conformation and function as a safeguard [7]. Here we show that a global structural switch can arise from single amino acid changes in cysteine-rich domains (CRD) of cnidarian nematocyst proteins. The ability of these CRDs to form two structures with different disulfide patterns from an identical cysteine pattern is distinctive [8]. By applying a structure-based mutagenesis approach, we demonstrate that a cysteine-rich domain can interconvert between two natively occurring domain structures via a bridge state containing both structures. Comparing cnidarian CRD sequences leads us to believe that the mutations we introduced to stabilize each structure reflect the birth of new protein folds in evolution.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Grzesiek)
UniBasel Contributors:Grzesiek, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0960-9822
e-ISSN:1879-0445
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Nov 2017 15:12
Deposited On:22 Mar 2012 13:21

Repository Staff Only: item control page