Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB

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Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB. / Guo, Zhong; Hou, Xiaomin; Goody, Roger S; Itzen, Aymelt.

In: J BIOL CHEM, Vol. 288, No. 45, 08.11.2013, p. 32466-74.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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@article{6944b5d86c0b4455894959326f2fff31,
title = "Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB",
abstract = "Small G-proteins of the Ras superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replacement of GDP by GTP. During nucleotide exchange, three distinct substrate·enzyme complexes occur: a ternary complex with GDP at the start of the reaction (G-protein·GEF·GDP), an intermediary nucleotide-free binary complex (G-protein·GEF), and a ternary GTP complex after productive G-protein activation (G-protein·GEF·GTP). Here, we show structural snapshots of the full nucleotide exchange reaction sequence together with the G-protein substrates and products using Rabin8/GRAB (GEF) and Rab8 (G-protein) as a model system. Together with a thorough enzymatic characterization, our data provide a detailed view into the mechanism of Rabin8/GRAB-mediated nucleotide exchange. ",
keywords = "Catalysis, Guanosine Triphosphate, Humans, Multienzyme Complexes, Protein-Serine-Threonine Kinases, Recombinant Proteins, rab GTP-Binding Proteins, rab3A GTP-Binding Protein, Journal Article, Research Support, Non-U.S. Gov't",
author = "Zhong Guo and Xiaomin Hou and Goody, {Roger S} and Aymelt Itzen",
year = "2013",
month = nov,
day = "8",
doi = "10.1074/jbc.M113.498329",
language = "English",
volume = "288",
pages = "32466--74",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "45",

}

RIS

TY - JOUR

T1 - Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB

AU - Guo, Zhong

AU - Hou, Xiaomin

AU - Goody, Roger S

AU - Itzen, Aymelt

PY - 2013/11/8

Y1 - 2013/11/8

N2 - Small G-proteins of the Ras superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replacement of GDP by GTP. During nucleotide exchange, three distinct substrate·enzyme complexes occur: a ternary complex with GDP at the start of the reaction (G-protein·GEF·GDP), an intermediary nucleotide-free binary complex (G-protein·GEF), and a ternary GTP complex after productive G-protein activation (G-protein·GEF·GTP). Here, we show structural snapshots of the full nucleotide exchange reaction sequence together with the G-protein substrates and products using Rabin8/GRAB (GEF) and Rab8 (G-protein) as a model system. Together with a thorough enzymatic characterization, our data provide a detailed view into the mechanism of Rabin8/GRAB-mediated nucleotide exchange.

AB - Small G-proteins of the Ras superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replacement of GDP by GTP. During nucleotide exchange, three distinct substrate·enzyme complexes occur: a ternary complex with GDP at the start of the reaction (G-protein·GEF·GDP), an intermediary nucleotide-free binary complex (G-protein·GEF), and a ternary GTP complex after productive G-protein activation (G-protein·GEF·GTP). Here, we show structural snapshots of the full nucleotide exchange reaction sequence together with the G-protein substrates and products using Rabin8/GRAB (GEF) and Rab8 (G-protein) as a model system. Together with a thorough enzymatic characterization, our data provide a detailed view into the mechanism of Rabin8/GRAB-mediated nucleotide exchange.

KW - Catalysis

KW - Guanosine Triphosphate

KW - Humans

KW - Multienzyme Complexes

KW - Protein-Serine-Threonine Kinases

KW - Recombinant Proteins

KW - rab GTP-Binding Proteins

KW - rab3A GTP-Binding Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1074/jbc.M113.498329

DO - 10.1074/jbc.M113.498329

M3 - SCORING: Journal article

C2 - 24072714

VL - 288

SP - 32466

EP - 32474

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 45

ER -