Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

Savita Bhutoria, Ganjam V. Kalpana, Seetharama A. Acharya

Research output: Contribution to journalArticle

Abstract

The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1.

Original languageEnglish (US)
Pages (from-to)1593-1604
Number of pages12
JournalProtein Science
DOIs
Publication statusPublished - Sep 1 2016

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Keywords

  • integrase interactor (INI)1/hSNF5
  • protein structure modeling
  • repeats
  • SNF5
  • ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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