A novel TPR-BEN domain interaction mediates PICH-BEND3 association

TY - JOUR

T1 - A novel TPR-BEN domain interaction mediates PICH-BEND3 association

AU - Pitchai, Ganesha P

AU - Kaulich, Manuel

AU - Bizard, Anna H

AU - Mesa, Pablo

AU - Yao, Qi

AU - Sarlos, Kata

AU - Streicher, Werner W

AU - Nigg, Erich A

AU - Montoya, Guillermo

AU - Hickson, Ian D

N1 - © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2017/11/2

Y1 - 2017/11/2

N2 - PICH is a DNA translocase required for the maintenance of chromosome stability in human cells. Recent data indicate that PICH co-operates with topoisomerase II to suppress pathological chromosome missegregation through promoting the resolution of ultra-fine anaphase bridges (UFBs). Here, we identify the BEN domain-containing protein 3 (BEND3) as an interaction partner of PICH in human cells in mitosis. We have purified full length PICH and BEND3 and shown that they exhibit a functional biochemical interaction in vitro. We demonstrate that the PICH- BEND3 interaction occurs via a novel interface between a TPR domain in PICH and a BEN domain in BEND3, and have determined the crystal structure of this TPR-BEN complex at 2.2 A resolution. Based on the structure, we identified amino acids important for the TPR-BEN domain interaction, and for the functional interaction of the full-length proteins. Our data reveal a proposed new function for BEND3 in association with PICH, and the first example of a specific protein-protein interaction mediated by a BEN domain.

AB - PICH is a DNA translocase required for the maintenance of chromosome stability in human cells. Recent data indicate that PICH co-operates with topoisomerase II to suppress pathological chromosome missegregation through promoting the resolution of ultra-fine anaphase bridges (UFBs). Here, we identify the BEN domain-containing protein 3 (BEND3) as an interaction partner of PICH in human cells in mitosis. We have purified full length PICH and BEND3 and shown that they exhibit a functional biochemical interaction in vitro. We demonstrate that the PICH- BEND3 interaction occurs via a novel interface between a TPR domain in PICH and a BEN domain in BEND3, and have determined the crystal structure of this TPR-BEN complex at 2.2 A resolution. Based on the structure, we identified amino acids important for the TPR-BEN domain interaction, and for the functional interaction of the full-length proteins. Our data reveal a proposed new function for BEND3 in association with PICH, and the first example of a specific protein-protein interaction mediated by a BEN domain.

KW - Journal Article

U2 - 10.1093/nar/gkx792

DO - 10.1093/nar/gkx792

M3 - Journal article

C2 - 28977671

SN - 0305-1048

VL - 19

SP - 11413

EP - 11424

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 2

ER -