TY - JOUR
T1 - Structural basis for nucleotide exchange on Gαi subunits and receptor coupling specificity
AU - Johnston, Christopher A.
AU - Siderovski, David P.
PY - 2007/2/6
Y1 - 2007/2/6
N2 - Heterotrimeric G proteins are molecular switches that relay information intracellularly in response to various extracellular signals. How ligand-activated G protein-coupled receptors act at a distance to exert exchange activity on the Gα nucleotide binding pocket is poorly understood. Here we describe the synergistic action of two peptides: one from the third intracellular loop of the D2 dopamine receptor (D2N), and a second, Gα-GDP-binding peptide (KB-752) that mimics the proposed role of Gβγ in receptor-promoted nucleotide exchange. The structure of both peptides in complex with Gαi1 suggests that conformational changes in the β3/α2 loop and β6 strand act in concert for efficient nucleotide exchange. Two key residues in the α4 helix were found to define a receptor/Gαi coupling specificity determinant.
AB - Heterotrimeric G proteins are molecular switches that relay information intracellularly in response to various extracellular signals. How ligand-activated G protein-coupled receptors act at a distance to exert exchange activity on the Gα nucleotide binding pocket is poorly understood. Here we describe the synergistic action of two peptides: one from the third intracellular loop of the D2 dopamine receptor (D2N), and a second, Gα-GDP-binding peptide (KB-752) that mimics the proposed role of Gβγ in receptor-promoted nucleotide exchange. The structure of both peptides in complex with Gαi1 suggests that conformational changes in the β3/α2 loop and β6 strand act in concert for efficient nucleotide exchange. Two key residues in the α4 helix were found to define a receptor/Gαi coupling specificity determinant.
KW - G protein-coupled receptors
KW - Guanine nucleotide exchange
KW - Heterotrimeric G proteins
UR - http://www.scopus.com/inward/record.url?scp=33846929083&partnerID=8YFLogxK
U2 - 10.1073/pnas.0608599104
DO - 10.1073/pnas.0608599104
M3 - Article
C2 - 17264214
AN - SCOPUS:33846929083
VL - 104
SP - 2001
EP - 2006
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6
ER -