8I6K

Structure of hMNDA HIN with dsDNA

Summary for 8I6K

• Entry DOI: 10.2210/pdb8i6k/pdb
• Descriptor: Myeloid cell nuclear differentiation antigen, DNA (5'-D(*GP*GP*CP*GP*CP*GP*CP*GP*CP*GP*CP*C)-3'), DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: complex, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 32067.42

Authors

Li, Y.L.,Jin, T.C. (deposition date: 2023-01-28, release date: 2023-07-19, Last modification date: 2024-05-29)

Primary citation

Li, Y.,Zhang, C.,Samad, A.,Zheng, P.,Li, Y.,Chen, F.,Jin, T.
Structural mechanism of dsDNA recognition by the hMNDA HIN domain: New insights into the DNA-binding model of a PYHIN protein.
Int.J.Biol.Macromol., 245:125461-125461, 2023

PubMed Abstract: The hematopoietic interferon-inducible nuclear (HIN) domain of the PYHIN family of proteins recognizes double-stranded DNA (dsDNA) through different dsDNA-binding modes. These modes apparently confer different roles upon these proteins in the regulation of innate immune responses, gene transcription, and apoptosis. Myeloid cell nuclear differentiation antigen (MNDA), a member of the human PYHIN family, binds DNA and regulates gene transcription in monocytes. However, the mechanism of DNA recognition and DNA-binding modes of human MNDA (hMNDA) remain unclear. Here, we determined the crystal structure of the hMNDA-HIN domain in complex with dsDNA at 2.4 Å resolution, and reveal that hMNDA-HIN binds to dsDNA in a sequence-independent manner. Structure and mutation studies indicated that hMNDA-HIN binds to dsDNA through a unique mode, involving two dsDNA-binding interfaces. Interface I exhibits an AIM2-like dsDNA-binding mode, and interface II has a previously unreported mode of dsDNA-binding. These results provide new insights into the DNA-binding modes of this PYHIN protein.

PubMed: 37348588
DOI: 10.1016/j.ijbiomac.2023.125461

Experimental method

X-RAY DIFFRACTION (2.4 Å)