Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide

被引:28
作者
Botuyan, MV
Mer, G
Yi, GS
Koth, CM
Case, DA
Edwards, AM
Chazin, WJ
Arrowsmith, CH
机构
[1] Univ Toronto, Ontario Canc Inst, Div Mol & Struct Biol, Toronto, ON M5G 2M9, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada
[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[4] Univ Toronto, Charles H Best Inst, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada
[5] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA
[6] Vanderbilt Univ, Dept Phys, Nashville, TN 37232 USA
[7] Vanderbilt Univ, Ctr Struct Biol, Nashville, TN 37232 USA
关键词
elongin; von Hippel-Lindau; NMR solution structure; ligand recognition; conformational change;
D O I
10.1006/jmbi.2001.4938
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
Elongin is a transcription elongation factor that stimulates the rate of elongation by suppressing transient pausing by RNA polymerase II at many sites along the DNA. It is heterotrimeric in mammals, consisting of elongins A, B and C subunits, and bears overall similarity to a class of E3 ubiquitin ligases known as SCF (Skp1-Cdc53 (cullin)-F-box) complexes. A subcomplex of elongins B and C is a target for negative regulation by the von Hippel-Lindau (VHL) tumor-suppressor protein. Elongin C from Saccharomyces cerevisiae, Elc1, exhibits high sequence similarity to mammalian elongin C. Using NMR spectroscopy we have determined the three-dimensional structure of Elc1 in complex with a human VHL peptide, VHL(157-171), representing the major Elc1 binding site. The bound VHL peptide is entirely helical. Elc1 utilizes two C-terminal helices and an intervening loop to form a binding groove that fits VHL(157-171). Chemical shift perturbation and dynamics analyses reveal that a global conformational change accompanies Elc1/VHL(157-171) complex formation. Moreover, the disappearance of conformational exchange phenomena on the microsecond to millisecond time scale within Elc1 upon VHL peptide binding suggests a role for slow internal motions in ligand recognition. (C) 2001 Academic Press.
引用
收藏
页码:177 / 186
页数:10
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