Modeling transient collapsed states of an unfolded protein to provide insights into early folding events

被引:96
作者
Felitsky, Daniel J. [1 ]
Lietzow, Michael A.
Dyson, H. Jane
Wright, Peter E.
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
关键词
buried surface area; diffusion-collision; entropy of loop closure; apomyoglobin folding; NMR spin labeling;
D O I
10.1073/pnas.0710641105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The primary driving force for protein folding is the sequestration of hydrophobic side chains from solvent water, but the means whereby the amino acid sequence directs the folding process to form the correct final folded state is not well understood. Measurements of NMR line broadening in spin-labeled samples of unfolded apomyoglobin at pH 2.3 have been used to derive a quantitative model for transient hydrophobic interactions between various sites in the polypeptide chain, as would occur during the initiation of protein folding. Local clusters of residues with high values for the parameter "average area buried upon folding" (AABUF) form foci not only for local contacts but for long-range interactions, the relative frequencies of which can be understood in terms of differences in the extent of reduction in chain configurational entropy that occurs upon formation of nonlocal contacts. These results complement the striking correlation previously observed between the kinetic folding process of apomyoglobin and the AABUF of its amino acid sequence [Nishimura C, Lietzow MA, Dyson HJ, Wright PE (2005) J Mol Biol 351:383-392]. For the acid-unfolded states of apomyoglobin, our approach identifies multiple distinct hydrophobic clusters of differing thermodynamic stability. The most structured of these clusters, although sparsely populated, have both native-like and nonnative character; the specificity of the transient long-range contacts observed in these states suggests that they play a key role in initiating chain collapse and folding.
引用
收藏
页码:6278 / 6283
页数:6
相关论文
共 29 条
[1]  
[Anonymous], 1976, SPIN LABELING THEORY
[2]   DIFFUSION-COLLISION MODEL FOR THE FOLDING KINETICS OF MYOGLOBIN [J].
BASHFORD, D ;
COHEN, FE ;
KARPLUS, M ;
KUNTZ, ID ;
WEAVER, DL .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1988, 4 (03) :211-227
[3]   Utilization of site-directed spin labeling and high-resolution heteronuclear nuclear magnetic resonance for global fold determination of large proteins with limited nuclear overhauser effect data [J].
Battiste, JL ;
Wagner, G .
BIOCHEMISTRY, 2000, 39 (18) :5355-5365
[4]   A structural model for unfolded proteins from residual dipolar couplings and small-angle x-ray scattering [J].
Bernadó, P ;
Blanchard, L ;
Timmins, P ;
Marion, D ;
Ruigrok, RWH ;
Blackledge, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (47) :17002-17007
[5]  
Bhattacharjee J. K., 1997, ARXIVCONDMAT9709345
[6]   NMRPIPE - A MULTIDIMENSIONAL SPECTRAL PROCESSING SYSTEM BASED ON UNIX PIPES [J].
DELAGLIO, F ;
GRZESIEK, S ;
VUISTER, GW ;
ZHU, G ;
PFEIFER, J ;
BAX, A .
JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (03) :277-293
[7]   The role of hydrophobic interactions in initiation and propagation of protein folding [J].
Dyson, H. Jane ;
Wright, Peter E. ;
Scheraga, Harold A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (35) :13057-13061
[8]  
Eliezer D, 1998, NAT STRUCT BIOL, V5, P148
[9]   Is apomyoglobin a molten globule? Structural characterization by NMR [J].
Eliezer, D ;
Wright, PE .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 263 (04) :531-538
[10]   PROTEIN CORE ASSEMBLY PROCESSES [J].
FIEBIG, KM ;
DILL, KA .
JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (04) :3475-3487