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In silico Structural characterization of podocin and assessment of nephrotic syndrome‐associated podocin mutants
Author(s) -
Mulukala Sandeep Kumar Narasimha,
Nishad Rajkishor,
Kolligundla Lakshmi Prasanna,
Saleem Moin A.,
Prabhu Nagu Prakash,
Pasupulati Anil Kumar
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1515
Subject(s) - podocin , podocyte , chemistry , nephrotic syndrome , biology , genetics , endocrinology , kidney , proteinuria
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. © 2016 IUBMB Life, 68(7):578–588, 2016