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

  • Nucleic Acids Res. 2017 Nov 2;45(19):11413-11424. doi: 10.1093/nar/gkx792.
Ganesha P Pitchai  1  2 ,  Manuel Kaulich  3 ,  Anna H Bizard  2 ,  Pablo Mesa  1 ,  Qi Yao  2 ,  Kata Sarlos  2 ,  Werner W Streicher  1 ,  Erich A Nigg  3 ,  Guillermo Montoya  1 ,  Ian D Hickson  2
Affiliations
  • 1. Novo Nordisk Foundation Center for Protein Research, Protein Structure & Function Programme, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • 2. Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
  • 3. Biozentrum, University of Basel, CH-4056, Basel, Switzerland.
PMID: 28977671 DOI: 10.1093/nar/gkx792
Abstract

PICH is a DNA translocase required for the maintenance of chromosome stability in human cells. Recent data indicate that PICH co-operates with Topoisomerase IIα 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 Å 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.