8YAP

Structure of human PALB2 coiled-coil domain

Summary for 8YAP

• Entry DOI: 10.2210/pdb8yap/pdb
• Descriptor: Partner and localizer of BRCA2 (1 entity in total)
• Functional Keywords: tumor suppressor, dna repair, homologous recombination, brca1, brca2, cancer, dna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 8890.52

Authors

Reddy, P.P.,Das, R. (deposition date: 2024-02-09, release date: 2025-02-12, Last modification date: 2025-04-02)

Primary citation

Reddy, P.P.,Phale, A.,Das, R.
Structural analysis of genetic variants of the human tumor suppressor PALB2 coiled-coil domain.
Biosci.Rep., 45:-, 2025

PubMed 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 interactions of the PALB2 coiled-coil domain. Our findings reveal a strong correlation between the structural impact of mutations and their efficiency in homologous recombination, suggesting that our approach can be applied to study other genetic variations in PALB2. These findings hold promise for improving genetic counseling and advancing cancer research.

PubMed: 39745016
DOI: 10.1042/BSR20241173

Experimental method

SOLUTION NMR