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A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1

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A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. / Hou, Xiaomin; Hagemann, Nina; Schoebel, Stefan; Blankenfeldt, Wulf; Goody, Roger S; Erdmann, Kai S; Itzen, Aymelt.

in: EMBO J, Jahrgang 30, Nr. 8, 20.04.2011, S. 1659-70.

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

Harvard

Hou, X, Hagemann, N, Schoebel, S, Blankenfeldt, W, Goody, RS, Erdmann, KS & Itzen, A 2011, 'A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1', EMBO J, Jg. 30, Nr. 8, S. 1659-70. https://doi.org/10.1038/emboj.2011.60

APA

Hou, X., Hagemann, N., Schoebel, S., Blankenfeldt, W., Goody, R. S., Erdmann, K. S., & Itzen, A. (2011). A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO J, 30(8), 1659-70. https://doi.org/10.1038/emboj.2011.60

Vancouver

Hou X, Hagemann N, Schoebel S, Blankenfeldt W, Goody RS, Erdmann KS et al. A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO J. 2011 Apr 20;30(8):1659-70. https://doi.org/10.1038/emboj.2011.60

Bibtex

@article{de1fafe5f02940f68e2f82dc3d75e768,
title = "A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1",
abstract = "The oculocerebrorenal syndrome of Lowe (OCRL), also called Lowe syndrome, is characterized by defects of the nervous system, the eye and the kidney. Lowe syndrome is a monogenetic X-linked disease caused by mutations of the inositol-5-phosphatase OCRL1. OCRL1 is a membrane-bound protein recruited to membranes via interaction with a variety of Rab proteins. The structural and kinetic basis of OCRL1 for the recognition of several Rab proteins is unknown. In this study, we report the crystal structure of the Rab-binding domain (RBD) of OCRL1 in complex with Rab8a and the kinetic binding analysis of OCRL1 with several Rab GTPases (Rab1b, Rab5a, Rab6a and Rab8a). In contrast to other effectors that bind their respective Rab predominantly via α-helical structure elements, the Rab-binding interface of OCRL1 consists mainly of the IgG-like β-strand structure of the ASPM-SPD-2-Hydin domain as well as one α-helix. Our results give a deeper structural understanding of disease-causing mutations of OCRL1 affecting Rab binding.",
keywords = "Cell Membrane, Crystallization, Crystallography, X-Ray, Fluorescent Antibody Technique, Humans, Immunoprecipitation, Mutation, Oculocerebrorenal Syndrome, Phosphoric Monoester Hydrolases, Protein Conformation, Protein Structure, Tertiary, rab GTP-Binding Proteins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Xiaomin Hou and Nina Hagemann and Stefan Schoebel and Wulf Blankenfeldt and Goody, {Roger S} and Erdmann, {Kai S} and Aymelt Itzen",
year = "2011",
month = apr,
day = "20",
doi = "10.1038/emboj.2011.60",
language = "English",
volume = "30",
pages = "1659--70",
journal = "EMBO J",
issn = "0261-4189",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1

AU - Hou, Xiaomin

AU - Hagemann, Nina

AU - Schoebel, Stefan

AU - Blankenfeldt, Wulf

AU - Goody, Roger S

AU - Erdmann, Kai S

AU - Itzen, Aymelt

PY - 2011/4/20

Y1 - 2011/4/20

N2 - The oculocerebrorenal syndrome of Lowe (OCRL), also called Lowe syndrome, is characterized by defects of the nervous system, the eye and the kidney. Lowe syndrome is a monogenetic X-linked disease caused by mutations of the inositol-5-phosphatase OCRL1. OCRL1 is a membrane-bound protein recruited to membranes via interaction with a variety of Rab proteins. The structural and kinetic basis of OCRL1 for the recognition of several Rab proteins is unknown. In this study, we report the crystal structure of the Rab-binding domain (RBD) of OCRL1 in complex with Rab8a and the kinetic binding analysis of OCRL1 with several Rab GTPases (Rab1b, Rab5a, Rab6a and Rab8a). In contrast to other effectors that bind their respective Rab predominantly via α-helical structure elements, the Rab-binding interface of OCRL1 consists mainly of the IgG-like β-strand structure of the ASPM-SPD-2-Hydin domain as well as one α-helix. Our results give a deeper structural understanding of disease-causing mutations of OCRL1 affecting Rab binding.

AB - The oculocerebrorenal syndrome of Lowe (OCRL), also called Lowe syndrome, is characterized by defects of the nervous system, the eye and the kidney. Lowe syndrome is a monogenetic X-linked disease caused by mutations of the inositol-5-phosphatase OCRL1. OCRL1 is a membrane-bound protein recruited to membranes via interaction with a variety of Rab proteins. The structural and kinetic basis of OCRL1 for the recognition of several Rab proteins is unknown. In this study, we report the crystal structure of the Rab-binding domain (RBD) of OCRL1 in complex with Rab8a and the kinetic binding analysis of OCRL1 with several Rab GTPases (Rab1b, Rab5a, Rab6a and Rab8a). In contrast to other effectors that bind their respective Rab predominantly via α-helical structure elements, the Rab-binding interface of OCRL1 consists mainly of the IgG-like β-strand structure of the ASPM-SPD-2-Hydin domain as well as one α-helix. Our results give a deeper structural understanding of disease-causing mutations of OCRL1 affecting Rab binding.

KW - Cell Membrane

KW - Crystallization

KW - Crystallography, X-Ray

KW - Fluorescent Antibody Technique

KW - Humans

KW - Immunoprecipitation

KW - Mutation

KW - Oculocerebrorenal Syndrome

KW - Phosphoric Monoester Hydrolases

KW - Protein Conformation

KW - Protein Structure, Tertiary

KW - rab GTP-Binding Proteins

KW - Journal Article

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

U2 - 10.1038/emboj.2011.60

DO - 10.1038/emboj.2011.60

M3 - SCORING: Journal article

C2 - 21378754

VL - 30

SP - 1659

EP - 1670

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 8

ER -