Structural properties of polyubiquitin chains in solution

被引:228
作者
Varadan, R
Walker, O
Pickart, C
Fushman, D
机构
[1] Univ Maryland, Dept Chem & Biochem, Ctr Biomol Struct & Org, College Pk, MD 20742 USA
[2] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA
关键词
ubiquitin; polyubiquitin chains; chemical shift mapping; domain orientation measurements; spin relaxation;
D O I
10.1016/S0022-2836(02)01198-1
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
Because polyubiquitin chain structure modulates Ub-mediated signaling, knowledge of the physiological conformations of chain signals should provide insights into specific recognition. Here, we characterized the solution conformations of K48-linked Ub(2) and Ub(4) using a combination of NMR techniques, including chemical shift mapping of the interdomain interface, domain orientation measurements on the basis of N-15 relaxation and residual dipolar couplings, and the solvent accessibility studies. Our data indicate a switch in the conformation of Ub(2), from open to closed, with increasing pH. The closed conformation features a well-defined interface that is related to, but distinguishable from, that observed in the Ub(2) crystal structure. This interface is dynamic in solution, such that important hydrophobic residues (L8, I44, V70) that are sequestered at the interface in the closed conformation may be accessible for direct interactions with recognition factors. Our results suggest that the distal two units of Ub(4), which is the minimum signal for efficient proteasomal degradation, may adopt the closed Ub(2) conformation. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:637 / 647
页数:11
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