BRCA1 RING domain cancer-predisposing mutations: structural consequences and effects on protein-protein interactions

PS Brzovic, JE Meza, MC King, RE Klevit - Journal of Biological Chemistry, 2001 - jbc.org
Cancer-predisposing missense mutations in the RING domain of BRCA1 primarily target Zn
2+-liganding residues. Here we report on the structural consequences of such mutations
introduced into the second Zn 2+ site (Site II) of the BRCA1 RING domain and their effect on
the interaction with the BARD1 RING domain. Each of the BRCA1 Site II mutants still interact
and form a stable heterodimer with BARD1. Limited proteolysis of BRCA1/BARD1
complexes, monitored by matrix-assisted laser desorption ionization time-of-flight …