1Q14

Structure and autoregulation of the Yeast Hst2 homolog of Sir2

(2003) Nat Struct Biol 10: 864-871

• PubMed: 14502267 Search on PubMed
• DOI: https://doi.org/10.1038/nsb978
• Primary Citation of Related Structures:  
  1Q14


• PubMed Abstract: 
  

  Yeast Hst2 (yHst2) is a member of the silencing information regulator 2 (Sir2) family of NAD(+)-dependent protein deacetylases that are implicated in transcriptional silencing, DNA repair, genome stability and longevity. The X-ray crystal structure of the full-length yHst2 protein reveals a central catalytic core domain fold that is characteristic of the other Sir2 homologs, and C- and N-terminal extensions that interact with the NAD(+) and acetyl-lysine substrate-binding sites, respectively, suggesting an autoregulatory function for these domains. Moreover, the N-terminal extension mediates formation of a homotrimer within the crystal lattice. Enzymatic and sedimentation equilibrium studies using deletion constructs of yHst2 support the involvement of the N- and C-terminal yHst2 regions and trimer formation in catalysis by yHst2. Together, these studies indicate that the sequence-divergent N- and C-terminal regions of the eukaryotic Sir2 proteins may have a particularly important role in their distinct substrate-binding properties, biological activities or both.

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Organizational Affiliation: 

The Wistar Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.