Premium
Mechanism of induced folding: Both folding before binding and binding before folding can be realized in staphylococcal nuclease mutants
Author(s) -
Onitsuka Masayoshi,
Kamikubo Hironari,
Yamazaki Yoichi,
Kataoka Mikio
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21978
Subject(s) - folding (dsp implementation) , protein folding , phi value analysis , downhill folding , biophysics , chemistry , kinetics , folding funnel , mutant , binding site , crystallography , biochemistry , biology , physics , quantum mechanics , gene , electrical engineering , engineering
A considerable number of functional proteins are unstructured under physiological condition. These “intrinsically disordered” proteins exhibit induced folding when they bind their targets. The induced folding comprises two elementary processes: folding and binding. Two mechanisms are possible for the induced folding: either folding before binding or binding before folding. We found that these two mechanisms can be distinguished by the target‐concentration dependence of folding kinetics. We also created two types of mutants of staphylococcal nuclease showing the different inhibitor‐concentration dependence of induced folding kinetics. One mutant obeys the scheme of binding before folding, while the other the folding before binding. This is the first experimental evidence demonstrating that both mechanisms are realized for a single protein. Binding before folding is possible, when the protein lacks essential nonlocal interaction to stabilize the native conformation. The results cast light on the protein folding mechanism involved in the intrinsically disordered proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.