PMID- 14622106
OWN - NLM
STAT- MEDLINE
DCOM- 20031218
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 87
IP  - 5
DP  - 2003 Dec
TI  - A point mutation uncouples transducin-alpha from the photoreceptor RGS and 
      effector proteins.
PG  - 1262-71
AB  - A novel gain-of-function mutation, R243Q, has been recently identified in the 
      Candida elegans Gqalpha protein EGL-30. The position corresponding to Arg243 in 
      EGL-30 is absolutely conserved among heterotrimeric G proteins. This mutation 
      appears to be the first gain-of-function mutation in the switch III region of 
      Galpha subunits. To investigate consequences of the R-->Q mutation we introduced 
      the corresponding R238Q mutation into transducin-like Gtalpha* subunit. The 
      mutant retained intact interactions with Gtbetagamma and rhodopsin but exhibited 
      a twofold reduction in the kcat value for guanosine 5'-triphosphate (GTP) 
      hydrolysis. The GTPase activity of R238Q was not accelerated by the RGS domain of 
      the visual GTPase-activating protein, RGS9-1. In addition, R238Q displayed a 
      significant impairment in the effector function. Our data and the crystal 
      structures of transducin suggest that the major reason for the reduced intrinsic 
      GTPase activity of R238Q and the lack of RGS9 function is the break of the 
      conserved ionic contact between Arg238 and Glu39, which apparently stabilizes the 
      transitional state for GTP hydrolysis. We hypothesize that the R243Q mutation in 
      EGL-30 severs the ionic interaction of Arg243 with Glu43, leading to a defective 
      inactivation of the mutant by the C. elegans RGS protein EAT-16.
FAU - Natochin, Michael
AU  - Natochin M
AD  - Department of Physiology and Biophysics, University of Iowa College of Medicine, 
      Iowa City, IA 52242, USA.
FAU - Artemyev, Nikolai O
AU  - Artemyev NO
LA  - eng
GR  - R01 EY 12682/EY/NEI 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  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Fungal Proteins)
RN  - 0 (RGS Proteins)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9009-81-8 (Rhodopsin)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
RN  - EC 3.6.5.1 (Transducin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Candida
MH  - Conserved Sequence
MH  - Enzyme Activation/genetics
MH  - Fungal Proteins/chemistry/*genetics/metabolism
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/genetics
MH  - Guanosine Triphosphate/chemistry
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Point Mutation
MH  - Protein Binding/genetics
MH  - Protein Folding
MH  - RGS Proteins/chemistry/*metabolism
MH  - Rhodopsin/chemistry/metabolism
MH  - Structure-Activity Relationship
MH  - Transducin/chemistry/*genetics/metabolism
EDAT- 2003/11/19 05:00
MHDA- 2003/12/19 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2003/12/19 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - 2103 [pii]
AID - 10.1046/j.1471-4159.2003.02103.x [doi]
PST - ppublish
SO  - J Neurochem. 2003 Dec;87(5):1262-71. doi: 10.1046/j.1471-4159.2003.02103.x.