Structural basis for activation of ARF GTPase: Mechanisms of guanine nucleotide exchange and GTP-myristoyl switching Journal Article
| Author: | Goldberg, J. |
| Article Title: | Structural basis for activation of ARF GTPase: Mechanisms of guanine nucleotide exchange and GTP-myristoyl switching |
| Abstract: | Ras-related GTPases are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. The crystal structure of the Sec7 domain GEF bound to nucleotide-free ARF1 GTPase has been determined at 2.8 Å resolution and the structure of ARF1 in the GTP- analog form determined at 1.6 Å resolution. The Sec7 domain binds to the switch regions of ARF1 and inserts residues directly into the GTPase active site. The interaction leaves the purine-binding site intact but perturbs the Mg2+ and phosphate groups to promote the dissociation of guanine nucleotides. The structure of ARF1 in the GTP-analog form closely resembles Ras, revealing a substantial rearrangement from the GDP conformation. The transition controls the exposure of the myristoylated N terminus, explaining how ARF GTPases couple the GDP-GTP conformational switch to membrane binding. |
| Keywords: | signal transduction; protein conformation; protein domain; gtp-binding proteins; enzyme activation; molecular sequence data; crystal structure; protein structure, tertiary; ras protein; binding sites; conformational transition; protein structure; guanosine triphosphate; phosphate; protein structure, secondary; dissociation; membrane binding; gtp phosphohydrolases; enzyme active site; magnesium ion; guanine nucleotide exchange factors; purine; yeasts; crystallography; fungal proteins; guanosine diphosphate; guanine nucleotide exchange factor; guanosine triphosphatase; myristic acid; myristylation; adp-ribosylation factor 1; adp-ribosylation factors; priority journal; article |
| Journal Title: | Cell |
| Volume: | 95 |
| Issue: | 2 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 1998-10-16 |
| Start Page: | 237 |
| End Page: | 248 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(00)81754-7 |
| PUBMED: | 9790530 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
