| Full text | |
| Author(s): |
Ferreira, Frederico M.
[1, 2]
;
Oliveira, Leandro C.
[3]
;
Germino, Gregory G.
[4]
;
Onuchic, Jose N.
[3]
;
Onuchic, Luiz F.
[1]
Total Authors: 5
|
| Affiliation: | [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
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 108, n. 24, p. 9833-9838, JUN 14 2011. |
| Web of Science Citations: | 9 |
| 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 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) | |
| FAPESP's process: | 06/03098-8 - Structural analysis of proteins related to autosomal dominant polycystic kidney disease |
| Grantee: | Frederico Moraes Ferreira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |