8J69

Crystal structure of HORMA domain-containing protein 1 (HORMAD1) from Homo sapiens

Summary for 8J69

• Entry DOI: 10.2210/pdb8j69/pdb
• Descriptor: HORMA domain-containing protein 1 (2 entities in total)
• Functional Keywords: horma domain-containing protein 1, adaptor, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 45259.47

Authors

Yang, X.Y.,Liu, X.H. (deposition date: 2023-04-25, release date: 2023-09-20, Last modification date: 2024-04-03)

Primary citation

Wang, H.,Xie, R.,Niu, F.,Yang, Q.,An, L.,Wu, C.,Liu, X.,Yang, X.
Structural and biochemical insights into the interaction mechanism underlying HORMAD1 and its partner proteins.
Structure, 31:1578-1588.e3, 2023

PubMed Abstract: The mammalian HORMA domain-containing protein 1 (HORMAD1) regulates DNA mismatch repair and homologous recombination (HR) repair in many cancers. Here, we show that the structure of human HORMAD1 adopts a self-closed conformation and displays an intra-molecular HORMA domain-closure motif interaction mode. Structural and biochemical data suggest that the interaction modes of the peptide motifs from HORMAD2 and MCM9 with HORMAD1 are highly similar to that of HORMAD1 own closure motif. The peptide motifs from diverse binding partners of HORMAD1 share a conserved Ser-Glu-Pro sequence. Additionally, structural comparison unveiled the HORMA-peptide motif interaction mode diversity among HORMA-containing proteins. Finally, cell-based assays revealed that this HORMA-closure motif interaction pattern contributes to DNA mismatch repair and is required for HORMAD1-dependent HR repair. Together, our results provide structural and biochemical insights into the common theme and functional plasticity of the HORMA domain-containing protein family, and also reveal a universal regulation mechanism for HORMAD1.

PubMed: 37794593
DOI: 10.1016/j.str.2023.09.006

Experimental method

X-RAY DIFFRACTION (2.67 Å)