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 journal › SCORING: Journal article › Research › peer-review
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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 -