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The Extracellular Juncture Domains in the Intimin Passenger Adopt a Constitutively Extended Conformation Inducing Restraints to Its Sphere of Action

59 Pages Posted: 14 Jul 2020 Publication Status: Review Complete

See all articles by Julia Weikum

Julia Weikum

University of Oslo - Membrane Transport Group

Alina Kulakova

Technical University of Denmark - Department of Chemistry

Giulio Tesei

University of Copenhagen - Structural Biolohy and NMR Laboratory

Shogo Yoshimoto

Nagoya University - Department of Biomolecular Engineering

Line Vejby Jægerum

University of Oslo - Membrane Transport Group

Monika Schütz

University of Tuebingen - Interfaculty Institute for Microbiology and Infection Medicine

Katsutoshi Hori

Nagoya University - Department of Biomolecular Engineering

Marie Skepö

Lund University - Division of Theoretical Chemistry

Pernille Harris

Technical University of Denmark - Department of Chemistry

Jack C. Leo

University of Oslo - Department of Biosciences

Jens Preben Preben Morth

University of Oslo - Membrane Transport Group

More...

Abstract

Enterohemorrhagic and enteropathogenic Escherichia coli are among the most important food-borne pathogens, posing a global health threat. The virulence factor intimin is essential for attachment of pathogenic E. coli to the intestinal host cell. Intimin consists of four extracellular bacterial immunoglobulin-like (Big) domains, D00-D2, extending into the fifth lectin subdomain (D3) that binds to the Tir-receptor on the host cell. Here, we present the crystal structures of the elusive D00-D0 domains at 1.5 Å and D0-D1 at 1.8 Å resolution that confirm that the passenger of intimin has five distinct domains. We describe that D00-D0 exhibits a higher degree of rigidity and D00 likely functions as a juncture domain at the outer membrane-extracellular medium interface. We conclude that D00 is a unique Big domain with a specific topology likely found in a broad range of other inverse autotransporters. The accumulated data allows us to model the complete passenger of intimin and propose functionality to the Big domains, D00-D0-D1, extending directly from the membrane.

Keywords: Intimin, Invasin, Inverse Autotransporter, X-ray crystallography, SAXS, MD simulations

Suggested Citation

Weikum, Julia and Kulakova, Alina and Tesei, Giulio and Yoshimoto, Shogo and Jægerum, Line Vejby and Schütz, Monika and Hori, Katsutoshi and Skepö, Marie and Harris, Pernille and Leo, Jack C. and Morth, Jens Preben Preben, The Extracellular Juncture Domains in the Intimin Passenger Adopt a Constitutively Extended Conformation Inducing Restraints to Its Sphere of Action. Available at SSRN: https://ssrn.com/abstract=3635798 or http://dx.doi.org/10.2139/ssrn.3635798
This version of the paper has not been formally peer reviewed.

Julia Weikum

University of Oslo - Membrane Transport Group ( email )

Norway

Alina Kulakova

Technical University of Denmark - Department of Chemistry

Anker Engelunds Vej 1
Building 101A
Lyngby, 2800
Denmark

Giulio Tesei

University of Copenhagen - Structural Biolohy and NMR Laboratory

Nørregade 10
Copenhagen, København DK-1165
Denmark

Shogo Yoshimoto

Nagoya University - Department of Biomolecular Engineering ( email )

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Line Vejby Jægerum

University of Oslo - Membrane Transport Group

Norway

Monika Schütz

University of Tuebingen - Interfaculty Institute for Microbiology and Infection Medicine

Wilhelmstr. 19
72074 Tuebingen, Baden Wuerttemberg 72074
Germany

Katsutoshi Hori

Nagoya University - Department of Biomolecular Engineering

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Marie Skepö

Lund University - Division of Theoretical Chemistry

Box 117
Lund, SC Skane S221 00
Sweden

Pernille Harris

Technical University of Denmark - Department of Chemistry

Anker Engelunds Vej 1
Building 101A
Lyngby, 2800
Denmark

Jack C. Leo

University of Oslo - Department of Biosciences

Oslo, N-0316
Norway

Jens Preben Preben Morth (Contact Author)

University of Oslo - Membrane Transport Group ( email )

Norway

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