Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain

Frederico M. Ferreira, Leandro C. Oliveira, Gregory G. Germino, José N. Onuchic, Luiz F. Onuchic

Research output: Contribution to journalArticle

Abstract

Mutations in PKD2 are responsible for approximately 15% of the autosomal dominant polycystic kidney disease cases. This gene encodes polycystin-2, a calcium-permeable cation channel whose C-terminal intracytosolic tail (PC2t) plays an important role in its interaction with a number of different proteins. In the present study, we have comprehensively evaluated the macromolecular assembly of PC2t homooligomer using a series of biophysical and biochemical analyses. Our studies, based on a new delimitation of PC2t, have revealed that it is capable of assembling as a homotetramer independently of any other portion of the molecule. Our data support this tetrameric arrangement in the presence and absence of calcium.Molecular dynamics simulations performed with a modified all-atoms structure-based model supported the PC2t tetrameric assembly, as well as how different populations are disposed in solution. The simulations demonstrated, indeed, that the bestscored structures are the ones compatible with a fourfold oligomeric state. These findings clarify the structural properties of PC2t domain and strongly support a homotetramer assembly of PC2.

Original languageEnglish (US)
Pages (from-to)9833-9838
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number24
DOIs
StatePublished - Jun 14 2011
Externally publishedYes

ASJC Scopus subject areas

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