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Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4

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Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4. / Itzen, Aymelt; Pylypenko, Olena; Goody, Roger S; Alexandrov, Kirill; Rak, Alexey.

in: EMBO J, Jahrgang 25, Nr. 7, 05.04.2006, S. 1445-55.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Itzen, A, Pylypenko, O, Goody, RS, Alexandrov, K & Rak, A 2006, 'Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4', EMBO J, Jg. 25, Nr. 7, S. 1445-55. https://doi.org/10.1038/sj.emboj.7601044

APA

Itzen, A., Pylypenko, O., Goody, R. S., Alexandrov, K., & Rak, A. (2006). Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4. EMBO J, 25(7), 1445-55. https://doi.org/10.1038/sj.emboj.7601044

Vancouver

Itzen A, Pylypenko O, Goody RS, Alexandrov K, Rak A. Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4. EMBO J. 2006 Apr 5;25(7):1445-55. https://doi.org/10.1038/sj.emboj.7601044

Bibtex

@article{0735c125cc944c99b1ef9d63ce9b3bbf,
title = "Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4",
abstract = "Rab GTPases function as essential regulators of vesicle transport in eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab proteins associated with the exocytic pathway and to have nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange factor that forms a long-lived nucleotide-free complex with RabGTPase. In contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of magnitude more slowly than comparable complexes. The crystal structure of the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the Switch I and interswitch regions of Rab8, forming an intermolecular beta-sheet. Complex formation results in dramatic structural changes of the Rab8 molecule, leading to unfolding of the nucleotide-binding site and surrounding structural elements, facilitating nucleotide release and slowing its rebinding. Coupling of nucleotide exchange activity to a cycle of GTPase unfolding and refolding represents a novel nucleotide exchange mechanism.",
keywords = "Amino Acid Sequence, Guanine Nucleotide Exchange Factors, Guanosine, Kinetics, Models, Molecular, Molecular Sequence Data, Nucleotides, Protein Binding, Protein Conformation, Protein Folding, rab GTP-Binding Proteins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Aymelt Itzen and Olena Pylypenko and Goody, {Roger S} and Kirill Alexandrov and Alexey Rak",
year = "2006",
month = apr,
day = "5",
doi = "10.1038/sj.emboj.7601044",
language = "English",
volume = "25",
pages = "1445--55",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4

AU - Itzen, Aymelt

AU - Pylypenko, Olena

AU - Goody, Roger S

AU - Alexandrov, Kirill

AU - Rak, Alexey

PY - 2006/4/5

Y1 - 2006/4/5

N2 - Rab GTPases function as essential regulators of vesicle transport in eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab proteins associated with the exocytic pathway and to have nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange factor that forms a long-lived nucleotide-free complex with RabGTPase. In contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of magnitude more slowly than comparable complexes. The crystal structure of the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the Switch I and interswitch regions of Rab8, forming an intermolecular beta-sheet. Complex formation results in dramatic structural changes of the Rab8 molecule, leading to unfolding of the nucleotide-binding site and surrounding structural elements, facilitating nucleotide release and slowing its rebinding. Coupling of nucleotide exchange activity to a cycle of GTPase unfolding and refolding represents a novel nucleotide exchange mechanism.

AB - Rab GTPases function as essential regulators of vesicle transport in eukaryotic cells. MSS4 was shown to stimulate nucleotide exchange on Rab proteins associated with the exocytic pathway and to have nucleotide-free-Rab chaperone activity. A detailed kinetic analysis of MSS4 interaction with Rab8 showed that MSS4 is a relatively slow exchange factor that forms a long-lived nucleotide-free complex with RabGTPase. In contrast to other characterized exchange factor-GTPase complexes, MSS4:Rab8 complex binds GTP faster than GDP, but still ca. 3 orders of magnitude more slowly than comparable complexes. The crystal structure of the nucleotide-free MSS4:Rab8 complex revealed that MSS4 binds to the Switch I and interswitch regions of Rab8, forming an intermolecular beta-sheet. Complex formation results in dramatic structural changes of the Rab8 molecule, leading to unfolding of the nucleotide-binding site and surrounding structural elements, facilitating nucleotide release and slowing its rebinding. Coupling of nucleotide exchange activity to a cycle of GTPase unfolding and refolding represents a novel nucleotide exchange mechanism.

KW - Amino Acid Sequence

KW - Guanine Nucleotide Exchange Factors

KW - Guanosine

KW - Kinetics

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Nucleotides

KW - Protein Binding

KW - Protein Conformation

KW - Protein Folding

KW - rab GTP-Binding Proteins

KW - Journal Article

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

U2 - 10.1038/sj.emboj.7601044

DO - 10.1038/sj.emboj.7601044

M3 - SCORING: Journal article

C2 - 16541104

VL - 25

SP - 1445

EP - 1455

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 7

ER -