7S4A

MRG15 complex with PALB2 peptide

Summary for 7S4A

• Entry DOI: 10.2210/pdb7s4a/pdb
• Descriptor: Mortality factor 4-like protein 1, Partner and localizer of BRCA2 (3 entities in total)
• Functional Keywords: complex, tumor suppressor, recombination mediator, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 53004.64

Authors

Korolev, S.,Deveryshetty, J. (deposition date: 2021-09-08, release date: 2022-05-04, Last modification date: 2023-10-18)

Primary citation

Redington, J.,Deveryshetty, J.,Kanikkannan, L.,Miller, I.,Korolev, S.
Structural Insight into the Mechanism of PALB2 Interaction with MRG15.
Genes (Basel), 12:-, 2021

PubMed Abstract: The tumor suppressor protein partner and localizer of BRCA2 (PALB2) orchestrates the interactions between breast cancer susceptibility proteins 1 and 2 (BRCA1, -2) that are critical for genome stability, homologous recombination (HR) and DNA repair. PALB2 mutations predispose patients to a spectrum of cancers, including breast and ovarian cancers. PALB2 localizes HR machinery to chromatin and links it with transcription through multiple DNA and protein interactions. This includes its interaction with MRG15 (Morf-related gene on chromosome 15), which is part of many transcription complexes, including the HAT-associated and the HDAC-associated complexes. This interaction is critical for PALB2 localization in actively transcribed genes, where transcription/replication conflicts lead to frequent replication stress and DNA breaks. We solved the crystal structure of the MRG15 MRG domain bound to the PALB2 peptide and investigated the effect of several PALB2 mutations, including patient-derived variants. PALB2 interacts with an extended surface of the MRG that is known to interact with other proteins. This, together with a nanomolar affinity, suggests that the binding of MRG15 partners, including PALB2, to this region is mutually exclusive. Breast cancer-related mutations of PALB2 cause only minor attenuation of the binding affinity. New data reveal the mechanism of PALB2-MRG15 binding, advancing our understanding of PALB2 function in chromosome maintenance and tumorigenesis.

PubMed: 34946951
DOI: 10.3390/genes12122002

Experimental method

X-RAY DIFFRACTION (2.693 Å)