1Y3A

Structure of G-Alpha-I1 bound to a GDP-selective peptide provides insight into guanine nucleotide exchange

Summary for 1Y3A

• Entry DOI: 10.2210/pdb1y3a/pdb
• Descriptor: Guanine nucleotide-binding protein G(i), alpha-1 subunit, KB752 peptide, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 160337.15

Authors

Johnston, C.A.,Willard, F.S.,Jezyk, M.R.,Fredericks, Z.,Bodor, E.T.,Jones, M.B.,Blaesius, R.,Harden, T.K.,Sondek, J.,Watts, V.J.,Ramer, J.K.,Siderovski, D.P. (deposition date: 2004-11-24, release date: 2005-07-12, Last modification date: 2023-08-23)

Primary citation

Johnston, C.A.,Willard, F.S.,Jezyk, M.R.,Fredericks, Z.,Bodor, E.T.,Jones, M.B.,Blaesius, R.,Watts, V.J.,Harden, T.K.,Sondek, J.,Ramer, J.K.,Siderovski, D.P.
Structure of G-Alpha-I1 bound to a GDP-selective peptide provides insight into guanine nucleotide exchange
Structure, 7:1069-1080, 2005

PubMed Abstract: Heterotrimeric G proteins are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive, GDP bound state and an active, GTP bound state. Under basal conditions, G proteins exist in the inactive, GDP bound state; thus, nucleotide exchange is crucial to the onset of signaling. Despite our understanding of G protein signaling pathways, the mechanism of nucleotide exchange remains elusive. We employed phage display technology to identify nucleotide state-dependent Galpha binding peptides. Herein, we report a GDP-selective Galpha binding peptide, KB-752, that enhances spontaneous nucleotide exchange of Galpha(i) subunits. Structural determination of the Galpha(i1)/peptide complex reveals unique changes in the Galpha switch regions predicted to enhance nucleotide exchange by creating a GDP dissociation route. Our results cast light onto a potential mechanism by which Galpha subunits adopt a conformation suitable for nucleotide exchange.

PubMed: 16004878
DOI: 10.1016/j.str.2005.04.007

Experimental method

X-RAY DIFFRACTION (2.5 Å)