Article
A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.
Nature communications - 5 Aug 2024
Knight Kevin M, Krumm Brian E, Kapolka Nicholas J, Ludlam W Grant, Cui Meng, Mani Sepehr, Prytkova Iya, Obarow Elizabeth G, Lefevre Tyler J, Wei Wenyuan, Ma Ning, Huang Xi-Ping, Fay Jonathan F, Vaidehi Nagarajan, Smrcka Alan V, Slesinger Paul A, Logothetis Diomedes E, Martemyanov Kirill A, Roth Bryan L, Dohlman Henrik G
Abstract excerpt
Many neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans. GαoK46E has a charge reversal that clashes with the phosphate groups of GDP and GTP. As anticipated, the purified protein...
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