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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Graziano, Brian R. Zheng, Wei Park, Eunyoung Li, Yiqun Eck, Michael J. Goode, Bruce L. Tu, Daqi |
| Description | Author Affiliation: Tu D ( Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.); |
| Abstract | Formin proteins and their associated factors cooperate to assemble unbranched actin filaments in diverse cellular structures. The Saccharomyces cerevisiae formin Bni1 and its associated nucleation-promoting factor (NPF) Bud6 generate actin cables and mediate polarized cell growth. Bud6 binds to both the tail of the formin and G-actin, thereby recruiting monomeric actin to the formin to create a nucleation seed. Here, we structurally and functionally dissect the nucleation-promoting C-terminal region of Bud6 into a Bni1-binding 'core' domain and a G-actin binding 'flank' domain. The â ¼2-Å resolution crystal structure of the Bud6 core domain reveals an elongated dimeric rod with a unique fold resembling a triple-helical coiled-coil. Binding and actin-assembly assays show that conserved residues on the surface of this domain mediate binding to Bni1 and are required for NPF activity. We find that the Bni1 dimer binds two Bud6 dimers and that the Bud6 flank binds a single G-actin molecule. These findings suggest a model in which a Bni1/Bud6 complex with a 2:4 subunit stoichiometry assembles a nucleation seed with Bud6 coordinating up to four actin subunits. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Microfilament Proteins Chemistry Saccharomyces Cerevisiae Proteins Actins Metabolism Amino Acid Sequence Binding, Competitive Conserved Sequence Crystallography, X-Ray Genetics Models, Anatomic Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutant Proteins Protein Interaction Domains And Motifs Protein Multimerization Recombinant Fusion Proteins Saccharomyces Cerevisiae Sequence Homology, Amino Acid Static Electricity Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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