TY - JOUR
T1 - The AXH domain adopts alternative folds
T2 - The solution structure of HBP1 AXH
AU - De Chiara, Cesira
AU - Menon, Rajesh P.
AU - Adinolfi, Salvatore
AU - De Boer, Jasper
AU - Ktistaki, Eleni
AU - Kelly, Geoff
AU - Calder, Lesley
AU - Kioussis, Dimitris
AU - Pastore, Annalisa
N1 - Funding Information:
The work was supported by the European EUROSCA grant. We wish to dedicate this work to the memory of our colleague Margie Nair.
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18944394158&partnerID=8YFLogxK
U2 - 10.1016/j.str.2005.02.016
DO - 10.1016/j.str.2005.02.016
M3 - Article
C2 - 15893665
AN - SCOPUS:18944394158
SN - 0969-2126
VL - 13
SP - 743
EP - 753
JO - Structure
JF - Structure
IS - 5
ER -