The AXH domain adopts alternative folds: The solution structure of HBP1 AXH

被引：33

作者：

de Chiara, C ^{[1
]}

Menon, RP ^{[1
]}

Adinolfi, S ^{[1
]}

de Boer, J ^{[1
]}

Ktistaki, E ^{[1
]}

Kelly, G ^{[1
]}

Calder, L ^{[1
]}

Kioussls, D ^{[1
]}

Pastore, A ^{[1
]}

机构：

[1] Natl Inst Med Res, London NW7 1AA, England

来源：

STRUCTURE | 2005年 / 13卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.str.2005.02.016

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：

AXH is a protein module identified in two unrelated families that comprise the transcriptional repressor HBP1 and ataxin-1 (ATX1), the protein responsible for spinocerebellar ataxia type-1 (SCA1). SCA1 is a neurodegenerative disorder associated with protein misfolding and formation of toxic intranuclear aggregates. We have solved the structure in solution of monomeric AXH from HBP1. The domain adopts a nonclassical permutation of an OB fold and binds nucleic acids, a function previously unidentified for this region of HBP1. Comparison of HBP1 AXH with the crystal structure of dimeric ATX1 AXH indicates that, despite the significant sequence homology, the two proteins have different topologies, suggesting that AXH has chameleon properties. We further demonstrate that HBP1 AXH remains monomeric, whereas the ATX1 dimer spontaneously aggregates and forms fibers. Our results describe an entirely novel, to our knowledge, example of a chameleon fold and suggest a link between these properties and the SCA1 pathogenesis.

引用

页码：743 / 753

页数：11

共 57 条

[1] AN ALTERNATIVE 3D-NMR TECHNIQUE FOR CORRELATING BACKBONE N-15 WITH SIDE-CHAIN H-BETA-RESONANCES IN LARGER PROTEINS [J].