PMID- 7481799 OWN - NLM STAT- MEDLINE DCOM- 19951213 LR - 20190618 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 270 IP - 5238 DP - 1995 Nov 10 TI - Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. PG - 954-60 AB - Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, Gi alpha 1. The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction. FAU - Mixon, M B AU - Mixon MB AD - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9050, USA. FAU - Lee, E AU - Lee E FAU - Coleman, D E AU - Coleman DE FAU - Berghuis, A M AU - Berghuis AM FAU - Gilman, A G AU - Gilman AG FAU - Sprang, S R AU - Sprang SR LA - eng GR - DK 46371/DK/NIDDK NIH HHS/United States GR - GM34497/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 146-91-8 (Guanosine Diphosphate) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 86-01-1 (Guanosine Triphosphate) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - I38ZP9992A (Magnesium) SB - IM CIN - Science. 1995 Nov 10;270(5238):933-4. PMID: 7481796 MH - Binding Sites MH - Crystallography, X-Ray MH - GTP-Binding Proteins/*chemistry/metabolism MH - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism MH - Guanosine Diphosphate/*metabolism MH - Guanosine Triphosphate/*metabolism MH - Hydrogen Bonding MH - Hydrolysis MH - Magnesium/metabolism MH - Models, Molecular MH - *Protein Conformation MH - Protein Structure, Secondary MH - *Protein Structure, Tertiary EDAT- 1995/11/10 00:00 MHDA- 1995/11/10 00:01 CRDT- 1995/11/10 00:00 PHST- 1995/11/10 00:00 [pubmed] PHST- 1995/11/10 00:01 [medline] PHST- 1995/11/10 00:00 [entrez] AID - 10.1126/science.270.5238.954 [doi] PST - ppublish SO - Science. 1995 Nov 10;270(5238):954-60. doi: 10.1126/science.270.5238.954.