RT Journal Article
T1 ATXN1 N-terminal region explains the binding differences of wild-type and expanded forms
A1 Rocha, Sara
A1 Vieira, Jorge
A1 Vázquez González, Noé
A1 López Fernández, Hugo
A1 Fernández Riverola, Florentino
A1 Reboiro Jato, Miguel
A1 Sousa, André D.
A1 Vieira, Cristina P.
K1 32 Ciencias Médicas
K1 2302.27 Proteínas
K1 2410.07 Genética Humana
AB BackgroundWild-type (wt) polyglutamine (polyQ) regions are implicated in stabilization of protein-protein interactions (PPI). Pathological polyQ expansion, such as that in human Ataxin-1 (ATXN1), that causes spinocerebellar ataxia type 1 (SCA1), results in abnormal PPI. For ATXN1 a larger number of interactors has been reported for the expanded (82Q) than the wt (29Q) protein.MethodsTo understand how the expanded polyQ affects PPI, protein structures were predicted for wt and expanded ATXN1, as well as, for 71 ATXN1 interactors. Then, the binding surfaces of wt and expanded ATXN1 with the reported interactors were inferred.ResultsOur data supports that the polyQ expansion alters the ATXN1 conformation and that it enhances the strength of interaction with ATXN1 partners. For both ATXN1 variants, the number of residues at the predicted binding interface are greater after the polyQ, mainly due to the AXH domain. Moreover, the difference in the interaction strength of the ATXN1 variants was due to an increase in the number of interactions at the N-terminal region, before the polyQ, for the expanded form.ConclusionsThere are three regions at the AXH domain that are essential for ATXN1 PPI. The N-terminal region is responsible for the strength of the PPI with the ATXN1 variants. How the predicted motifs in this region affect PPI is discussed, in the context of ATXN1 post-transcriptional modifications.
PB BMC Medical Genomics
SN 17558794
YR 2019
FD 2019-10-26
LK http://hdl.handle.net/11093/4169
UL http://hdl.handle.net/11093/4169
LA eng
NO BMC Medical Genomics, 12(1): 145 (2019)
NO Xunta de Galicia | Ref. ED481B 2016/068–0
DS Investigo
RD 23-ene-2025