In silico Structural characterization of podocin and assessment of nephrotic syndrome-associated podocin mutants

Sandeep Kumar Narasimha Mulukala, Rajkishor Nishad, Lakshmi Prasanna Kolligundla, Moin A. Saleem, Nagu Prakash Prabhu, Anil Kumar Pasupulati*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
237 Downloads (Pure)

Abstract

Nephrotic syndrome (NS) is manifested by hyperproteinuria, hypoalbuminemia, and edema. NPHS2 that encodes podocin was found to have most mutations among the genes that are involved in the pathophysiology of NS. Podocin, an integral membrane protein belonging to stomatin family, is expressed exclusively in podocytes and is localized to slit-diaphragm (SD). Mutations in podocin are known to be associated with steroid-resistant NS and rapid progression to end-stage renal disease, thus signifying its role in maintaining SD integrity and podocyte function. The structural insights of podocin are not known, and the precise mechanism by which podocin contributes to the architecture of SD is yet to be elucidated. In this study, we deduced a model for human podocin, discussed the details of transmembrane localization and intrinsically unstructured regions, and provide an understanding of how podocin interacts with other SD components. Intraprotein interactions were assessed in wild-type podocin and in some of its mutants that are associated with idiopathic NS. Mutations in podocin alter the innate intraprotein interactions affecting the native structure of podocin and its ability to form critical complex with subpodocyte proteins.

Original languageEnglish
Pages (from-to)578-588
Number of pages11
JournalIUBMB Life
Volume68
Issue number7
Early online date18 May 2016
DOIs
Publication statusPublished - 20 Jun 2016

Keywords

  • molecular modeling
  • nephrotic syndrome
  • podocin
  • podocytes
  • proteinuria
  • slit diaphragm

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