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Nat Commun. 2018 Nov 6;9(1):4635. doi: 10.1038/s41467-018-07035-x.

Structural basis of Gip1 for cytosolic sequestration of G protein in wide-range chemotaxis.

Author information

1
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan.
2
Center for Biosystems Dynamics Research (BDR), RIKEN, Suita, Osaka, 565-0874, Japan.
3
Department of Life Science, Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun, Hyogo, 678-1297, Japan.
4
Center for Biosystems Dynamics Research (BDR), RIKEN, Suita, Osaka, 565-0874, Japan. ykamimur@riken.jp.
5
Institute for Protein Research, Osaka University, Suita, 565-0871, Japan.
6
Advanced Photon Technology Division, RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo, 679-5148, Japan.
7
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan. masahiroueda@fbs.osaka-u.ac.jp.
8
Center for Biosystems Dynamics Research (BDR), RIKEN, Suita, Osaka, 565-0874, Japan. masahiroueda@fbs.osaka-u.ac.jp.

Abstract

G protein interacting protein 1 (Gip1) binds and sequesters heterotrimeric G proteins in the cytosolic pool, thus regulating G protein-coupled receptor (GPCR) signalling for eukaryotic chemotaxis. Here, we report the underlying structural basis of Gip1 function. The crystal structure reveals that the region of Gip1 that binds to the G protein has a cylinder-like fold with a central hydrophobic cavity composed of six α-helices. Mutagenesis and biochemical analyses indicate that the hydrophobic cavity and the hydrogen bond network at the entrance of the cavity are essential for complex formation with the geranylgeranyl modification on the Gγ subunit. Mutations of the cavity impair G protein sequestration and translocation to the membrane from the cytosol upon receptor stimulation, leading to defects in chemotaxis at higher chemoattractant concentrations. These results demonstrate that the Gip1-dependent regulation of G protein shuttling ensures wide-range gradient sensing in eukaryotic chemotaxis.

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