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PMID: 20949063 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.

PloS one ·Vol. 5 ·No. 10 ·2010-10-07 ·Pages e13202

Song AX, Zhou CJ, Peng Y, Gao XC, Zhou ZR, Fu QS, Hong J, Lin DH, Hu HY

Abstract

The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists of two α-helices and a flexible linker, whereas that of the Ub-bound form is much more compact with hydrophobic contacts between the two helices. NMR dynamics indicates that the flexible linker becomes rigid when AT3-UIM12 binds with Ub. Isothermal titration calorimetry and NMR titration demonstrate that AT3-UIM12 binds diUb with two distinct affinities, and the linker plays a critical role in association of the two helices in diUb binding. These results provide an implication that the tandem UIM12 interacts with Ub or diUb in a cooperative manner through an allosteric effect and dynamics change of the linker region, which might be related to its recognitions with various Ub chains and ubiquitinated substrates.

MeSH Terms
Ataxin-3 Models, Molecular Nerve Tissue Proteins/chemistry,metabolism Nuclear Magnetic Resonance, Biomolecular Nuclear Proteins/chemistry,metabolism Protein Binding Protein Conformation Repressor Proteins/chemistry,metabolism Ubiquitin/metabolism
Chemicals
Nerve Tissue Proteins Nuclear Proteins Repressor Proteins Ubiquitin ATXN3 protein, human Ataxin-3
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Song Ai-Xin
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Zhou Chen-Jie
Peng Yu
Gao Xue-Chao
Zhou Zi-Ren
Fu Qing-Shan
Hong Jing
Lin Dong-Hai
Hu Hong-Yu
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0013202
Published
2010-10-07
Epub
2010-00-07
Pages
e13202
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2951365
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0013202 PMC Full Text View journal details
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