Lee J, Blaber SI, Dubey VK, Blaber M.
J Mol Biol. 2011 Apr 15;407(5):744-63.
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306-4300, USA.
Abstract
Fibroblast growth factor-1, a member of the 3-fold symmetric Beta-trefoil fold, was subjected to a series of symmetric constraint mutations in a process termed “top-down symmetric deconstruction.” The mutations enforced a cumulative exact 3-fold symmetry upon symmetrically equivalent positions within the protein and were combined with a stability screen. This process culminated in a Beta-trefoil protein with exact 3-fold primary-structure symmetry that exhibited excellent folding and stability properties. Subsequent fragmentation of the repeating primary-structure motif yielded a 42-residue polypeptide capable of spontaneous assembly as a homotrimer, producing a thermostable Beta-trefoil architecture. The results show that despite pronounced reduction in sequence complexity, pure symmetry in the design of a foldable, thermostable Beta-trefoil fold is possible. The top-down symmetric deconstruction approach provides a novel alternative means to successfully identify a useful polypeptide “building block” for subsequent “bottom-up” de novo design of target protein architecture.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Additional information:
This report describes in detail the development of the novel “top-down symmetric deconstruction” method of protein design and its application in the successful creation of a 42-residue polypeptide able to symmetrically self-assemble into a Beta -trefoil protein architecture. This report has been selected by Faculty of 1000 as one of the top 2% of published articles in biology and medicine.
