Molecular mechanism and structural basis of gain-of-function of STAT1 caused by pathogenic R274Q mutation.

ABSTRACT: Gain-of-function (GOF) mutations in the STAT1 gene are critical for the onset of chronic mucocutaneous candidiasis (CMC) disease. However, the molecular basis for the gain of STAT1 function remains largely unclear. Here, we investigated the structural features of STAT1 GOF residues to better understand the impact of these pathogenic mutations. We constructed STAT1 alanine mutants of the α3 helix residues of the coiled-coil domain, which are frequently found in CMC pathogenic mutations, and measured their transcriptional activities. Most of the identified GOF residues were located inside the coiled-coil domain stem structure or at the protein surface of the anti-parallel dimer interface. Unlike those, Arg-274 was adjacent to the DNA-binding domain. In addition, Arg-274

SUBMITTER: Fujiki R 

PROVIDER: S-EPMC5391754 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature