Premium
Understanding the sequence determinants of conformational switching using protein design
Author(s) -
Dalal Seema,
Regan Lynne
Publication year - 2000
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.9.9.1651
Subject(s) - protein design , sequence (biology) , computational biology , protein structure , protein folding , chemistry , biophysics , genetics , biology , biochemistry
Abstract An important goal of protein design is to understand the forces that stabilize a particular fold in preference to alternative folds. Here, we describe an extension of earlier studies in which we successfully designed a stable, native‐like helical protein that is 50% identical in sequence to a predominantly β‐sheet protein, the B1 domain of Streptococcal IgG‐binding protein G. We report the characteristics of a series of variants of our original design that have even higher sequence identity to the B1 domain. Their properties illustrate the extent to which protein stability and conformation can be modulated through careful manipulation of key amino acid residues. Our results have implications for understanding conformational change phenomena of central biological importance and in probing the malleability of the sequence/structure relationship.