Unfolded state of polyalanine is a segmented polyproline II helix

Proteins: Structure, Function and Bioinformatics - Tập 55 Số 3 - Trang 493-501 - 2004
Alex Kentsis1, Mihaly Mezei1, Tatyana Gindin1, Roman Osman1
1Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, New York

Tóm tắt

AbstractDefinition of the unfolded state of proteins is essential for understanding their stability and folding on biological timescales. Here, we find that under near physiological conditions the configurational ensemble of the unfolded state of the simplest protein structure, polyalanine α‐helix, cannot be described by the commonly used Flory random coil model, in which configurational probabilities are derived from conformational preferences of individual residues. We utilize novel effectively ergodic sampling algorithms in the presence of explicit aqueous solvation, and observe water‐mediated formation of polyproline II helical (PII) structure in the natively unfolded state of polyalanine, and its facilitation of α‐helix formation in longer peptides. The segmented PII helical coil preorganizes the unfolded state ensemble for folding pathway entry by reducing the conformational space available to the diffusive search. Thus, as much as half of the folding search in polyalanine is accomplished by preorganization of the unfolded state. Proteins 2004. © 2004 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1051/jcp/1968650044

10.1016/S0968-0004(02)00012-9

10.1002/(SICI)1097-0134(199604)24:4<413::AID-PROT1>3.0.CO;2-F

10.1016/S0968-0004(98)01346-2

10.1146/annurev.biophys.29.1.327

Aune KC, 1967, Evidence for residual structure in acid‐ and heat‐denatured proteins, J Biol Chem, 242, 4486, 10.1016/S0021-9258(18)99563-3

10.1002/bip.1968.360060911

10.1021/jp022445a

10.1063/1.1336807

10.1021/ja027381w

10.1073/pnas.112193999

10.1002/bip.1969.360080514

10.1002/bip.360311202

10.1016/0022-2836(92)90264-K

10.1021/bi00053a005

10.1103/PhysRevLett.85.2637

10.1002/1097-0134(20010101)42:1<77::AID-PROT80>3.0.CO;2-#

10.1016/S0006-3495(98)77709-4

GarciaAE.Characterization of non‐alpha helical conformations in Ala peptides.2003. Submitted for publication.

10.1073/pnas.042496899

10.1016/S0022-2836(03)00765-4

10.1021/ja990056x

10.1021/jp973084f

10.1063/1.445869

10.1111/j.1432-1033.1986.tb09653.x

10.1016/S0006-3495(03)74900-5

10.1016/0021-9991(81)90141-8

10.1063/1.1539839

10.1016/S0006-3495(00)76274-6

10.1021/ja00070a024

10.1007/978-1-4757-1598-9

10.1080/08927028808080954

10.1002/prot.340230211

10.1073/pnas.032665199

Mezei M, 2003, The solvation free energy of the peptide backbone is strongly conformation‐dependent, Proteins

10.1110/ps.8.6.1166

10.1021/ma60026a016

10.1021/bi00120a001

10.1021/j150570a005

10.1063/1.1730390

10.1063/1.1731802

10.1007/BF02980577

10.1021/ja00145a022

10.1073/pnas.052700099

10.1073/pnas.96.11.6031

10.1073/pnas.97.23.12565

10.1146/annurev.physchem.48.1.545

10.1146/annurev.physchem.52.1.499

10.1038/nature01060

10.1016/S0022-2836(02)01029-X

10.1016/S0022-2836(03)00519-9

10.1080/07391102.1989.10508502

Thông tin
Thông tin xuất bản

Proteins: Structure, Function and Bioinformatics

Tập 55 Số 3

493-501

Thông tin tác giả