Hydrophobic interactions at the Ccap position of the C-capping motif of α-helices

被引:36
作者
Ermolenko, DN
Thomas, ST
Aurora, R
Gronenborn, AM
Makhatadze, GI
机构
[1] Penn State Univ, Coll Med, Dept Biochem & Mol Biol H171, Hershey, PA 17033 USA
[2] Russian Acad Sci, AN Bakh Biochem Inst, Moscow 117071, Russia
[3] Pharmacia Corp, Computat Biol Grp, St Louis, MO 63017 USA
[4] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA
关键词
helix termination; C-capping motifs; statistical analysis; hydrophobic interactions; differential scanning calorimetry;
D O I
10.1016/S0022-2836(02)00734-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the possible role of residues at the Ccap position in an alpha-helix on protein stability. A set of 431 protein a.-helices containing a C'-Gly from the Protein Data Bank (PDB) was analyzed, and the normalized frequencies for finding particular residues at the Ccap position, the average fraction of buried surface area, and the hydrogen bonding patterns of the Ccap residue side-chain were calculated. We found that on average the Ccap position is 70% buried and noted a significant correlation (R = 0.8) between the relative burial of this residue and its hydrophobicity as defined by the Gibbs energy of transfer from octanol or cyclohexane to water. Ccap residues with polar side-chains are commonly involved in hydrogen bonding. The hydrogen bonding pattern is such that, the longer side-chains of Glu, Gln, Arg, Lys, His form hydrogen bonds with residues distal (>+/-4) in sequence, while the shorter side-chains of Asp, Asn, Ser, Thr exhibit hydrogen bonds with residues close in sequence (<±4), mainly involving backbone atoms. Experimentally we determined the thermodynamic propensities of residues at the Ccap position using the protein ubiquitin as a model system. We observed a large variation in the stability of the ubiquitin variants depending on the nature of the Ccap residue. Furthermore, the measured changes in stability of the ubiquitin variants correlate with the hydrophobicity of the Ccap residue. The experimental results, together with the statistical analysis of protein structures from the PDB, indicate that the key hydrophobic capping interactions between a helical residue (C3 or C4) and a residue outside the helix (C&DPRIME;, C3' or C4') are frequently enhanced by the hydrophobic interactions with Ccap residues. (C) 2002 Elsevier Science Ltd. All rights reserved.
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页码:123 / 135
页数:13
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