PMID- 10360181 OWN - NLM STAT- MEDLINE DCOM- 19990617 LR - 20210507 IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 3 IP - 5 DP - 1999 May TI - A molecular mechanism for the phosphorylation-dependent regulation of heterotrimeric G proteins by phosducin. PG - 649-60 AB - Visual signal transduction is a nearly noise-free process that is exquisitely well regulated over a wide dynamic range of light intensity. A key component in dark/light adaptation is phosducin, a phosphorylatable protein that modulates the amount of transducin heterotrimer (Gt alpha beta gamma) available through sequestration of the beta gamma subunits (Gt beta gamma). The structure of the phosphophosducin/Gt beta gamma complex combined with mutational and biophysical analysis provides a stereochemical mechanism for the regulation of the phosducin-Gt beta gamma interaction. Phosphorylation of serine 73 causes an order-to-disorder transition of a 20-residue stretch, including the phosphorylation site, by disrupting a helix-capping motif. This transition disrupts phosducin's interface with Gt beta gamma, leading to the release of unencumbered Gt beta gamma, which reassociates with the membrane and Gt alpha to form a signaling-competent Gt alpha beta gamma heterotrimer. FAU - Gaudet, R AU - Gaudet R AD - Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06511, USA. FAU - Savage, J R AU - Savage JR FAU - McLaughlin, J N AU - McLaughlin JN FAU - Willardson, B M AU - Willardson BM FAU - Sigler, P B AU - Sigler PB LA - eng SI - PDB/1B9X SI - PDB/1B9Y GR - GM22324/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 - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (Eye Proteins) RN - 0 (GTP-Binding Protein Regulators) RN - 0 (Phosphoproteins) RN - 0 (phosducin) RN - 452VLY9402 (Serine) RN - 9009-81-8 (Rhodopsin) RN - EC 2.7.- (Protein Kinases) RN - EC 3.4.- (Endopeptidases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM SB - S MH - Animals MH - Circular Dichroism MH - DNA Mutational Analysis MH - Endopeptidases/metabolism MH - Eye Proteins/chemistry/*genetics/metabolism MH - GTP-Binding Protein Regulators MH - GTP-Binding Proteins/*chemistry/*metabolism MH - Magnetic Resonance Spectroscopy MH - Molecular Sequence Data MH - Mutagenesis/physiology MH - Phosphoproteins/chemistry/*genetics/metabolism MH - Phosphorylation MH - Protein Kinases/metabolism MH - Protein Structure, Secondary MH - Protein Structure, Tertiary MH - Rats MH - Rhodopsin/metabolism MH - Serine MH - Vision, Ocular/*physiology EDAT- 1999/06/09 00:00 MHDA- 1999/06/09 00:01 CRDT- 1999/06/09 00:00 PHST- 1999/06/09 00:00 [pubmed] PHST- 1999/06/09 00:01 [medline] PHST- 1999/06/09 00:00 [entrez] AID - S1097-2765(00)80358-5 [pii] AID - 10.1016/s1097-2765(00)80358-5 [doi] PST - ppublish SO - Mol Cell. 1999 May;3(5):649-60. doi: 10.1016/s1097-2765(00)80358-5.