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Molecular Modeling of STAT5a tetramers

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NCI

COMPBIO-15

Authors

  • B.K. Sathyanarayana
  • W.J Leonard
  • BK Lee

Abstract

STAT5a is one of the seven Signal Transducer and Activator of Transcription proteins. In addition to forming dimers interacting with DNA after phosphorylation, it is also known to form tetramers bound to DNA. No structure of STAT5a dimer or tetramer in complex with DNA is yet available. We present the feasibility of forming STAT5a tetramers on DNA as two dimer complexes at various spacings on DNA. In order to do this, partial models of STAT5a complexed with DNA were built, based mostly on its homology with other STATs whose structures are known. Our tetramer models consist of two identical dimers of STAT5a placed on a single DNA chain at all possible base pair spacings between the dimers. The feasibility of forming a tetramer was assessed by estimating the probability that the two dimers interact through their N-terminal domains. The entire modeling was done using the Chimera graphics software. The estimated probabilities of tetramer-DNA complex formation were found to correlate with the experimentally measured frequency of tetramer binding sites in mouse genome as a function of the base pair separation between the two dimers of the tetramer of STAT5a.

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