Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain

Autor(es)

Ferreira, Frederico M. ^{[1, 2]} ; Oliveira, Leandro C. ^[3] ; Germino, Gregory G. ^[4] ; Onuchic, Jose N. ^[3] ; Onuchic, Luiz F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Div Nephrol, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Inst Heart, Immunol Lab, BR-05403900 Sao Paulo - Brazil

^[3] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 - USA

^[4] Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 108, n. 24, p. 9833-9838, JUN 14 2011.
• Citações Web of Science: 9

Resumo

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 best-scored 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. (AU)

• Processo FAPESP: 06/03098-8 - Análise estrutural de proteínas relacionadas à doença renal policística autossômica dominante
• Beneficiário: Frederico Moraes Ferreira
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado