Structural analysis of genetic variants of the human tumor suppressor PALB2 coiled-coil domain.

ABSTRACT: The tumor suppressor PALB2 is a key player in the homologous recombination (HR) pathway, functionally connecting BRCA proteins at the DNA damage site. PALB2 forms homodimers via its coiled-coil domain, and during HR, it forms a heterodimeric complex with BRCA1 using the same domain. However, the structural details of the human PALB2 coiled-coil domain are unknown. Several missense variants have been reported in the coiled-coil domain. The structure-function relationship of these variants is poorly understood, posing a challenge to genetic counseling. In this study, we present the solution structure of the human PALB2 coiled-coil domain, which forms an antiparallel homodimer. We then use this structure to investigate the impact of a few well-characterized missense mutations on the fold and

SUBMITTER: Reddy PP 

PROVIDER: S-EPMC12096946 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature