Document Detail


A novel DNA-binding mechanism for maf basic region-leucine zipper factors inferred from a MafA/DNA structure and binding specificities.
MedLine Citation:
PMID:  23148532     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
MafA is a proto-oncoprotein, and is critical for insulin gene expression in pancreatic β-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences, and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA/DNA complex. MafA forms base-specific hydrogen bonds with the flanking GC and central C0/G0 bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse-chase EMSA protocol revealed that mutating either the core-TGA or the flanking-TGC bases dramatically increases the binding off-rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively these results suggest a novel multi-step DNA-binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.
Authors:
Xun Lu; Gerald P Guanga; Cheng Wan; Robert Bennett Rose
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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