Structural insight into the XTACC3/XMAP215 interaction from CD and NMR studies on model peptides.

Abstract:

:TACC3 is a centrosomal adaptor protein that plays important roles during mitotic spindle assembly. It interacts with chTOG/XMAP215, which catalyzes the addition of tubulin dimers during microtubule growth. A 3D coiled-coil model for this interaction is available but the structural details are not well described. To characterize this interaction at atomic resolution, we have designed a simplified version of the system based on small peptides. Four different peptides have been studied by circular dichroism and nuclear magnetic resonance both singly and in all possible combinations; namely, five peptide pairs and two trios. In cosolvents, all single peptides tend to adopt helical conformations resembling those of the full-length protein. However, neither the single peptides nor pairs of peptides form coiled coils. We show that the simultaneous presence of all preformed helices is a prerequisite for binding. The simplest 3D model for the interaction, based on the NMR results, is proposed. Interestingly, the peptide's structure remains unaffected by mutations at essential positions for TACC3 activity. This suggests that the lack of interaction of this TACC3 mutant with XMAP does not correlate with changes in the protein structure and that specific interactions are likely responsible for the interaction and stability of the complex.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Partida-Hanon A,Treviño MA,Mompeán M,Jiménez MÁ,Bruix M

doi

10.1002/bip.23039

subject

Has Abstract

pub_date

2017-11-01 00:00:00

issue

11

eissn

0006-3525

issn

1097-0282

journal_volume

107

pub_type

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