Details

Autor(en) / Beteiligte

• Li, Yuelong
• Zhang, Caiying
• Samad, Abdus
• Zheng, Peiyi
• Li, Yajuan
• Chen, Feng
• Jin, Tengchuan

Titel

Structural mechanism of dsDNA recognition by the hMNDA HIN domain: New insights into the DNA-binding model of a PYHIN protein

Ist Teil von

• International journal of biological macromolecules, 2023-08, Vol.245, p.125461-125461, Article 125461

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •MNDA, a PYHIN protein, binds DNA and regulates gene transcription in monocytes.•Mechanism of DNA recognition and DNA-binding modes of hMNDA were investigated.•Crystal structure of the hMNDA–HIN complexed with dsDNA at 2.4 Å was determined.•hMNDA–HIN binds to dsDNA in a sequence-independent manner.•Binding involves two interfaces, one of which has a novel binding mode.