Structure of the type VI secretion system contractile sheath.
Bacteria use rapid contraction of a long sheath of the type VI secretion system (T6SS) to deliver effectors into a target cell. Here, we present an atomic-resolution structure of a native contracted Vibrio cholerae sheath determined by cryo-electron microscopy. The sheath subunits, composed of tightly interacting proteins VipA and VipB, assemble into a six-start helix. The helix is stabilized by a core domain assembled from four β strands donated by one VipA and two VipB molecules. The fold of inner and middle layers is conserved between T6SS and phage sheaths. However, the structure of the outer layer is distinct and suggests a mechanism of interaction of the bacterial sheath with an accessory ATPase, ClpV, that facilitates multiple rounds of effector delivery. Our results provide a mechanistic insight into assembly of contractile nanomachines that bacteria and phages use to translocate macromolecules across membranes.
Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Mikhail
M
Kudryashev
Department of Biochemistry, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; Graduate Program in Biological Physics, Structure and Design, University of Washington, Box 357350, Seattle, WA 98195, USA.
Ray Yu-Ruei
RY
Wang
Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Maximilian
M
Brackmann
Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Sebastian
S
Scherer
Focal Area Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Timm
T
Maier
Department of Biochemistry, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
David
D
Baker
Department of Biochemistry, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
Frank
F
DiMaio
Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Henning
H
Stahlberg
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: egelman@virginia.edu.
Edward H
EH
Egelman
Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: marek.basler@unibas.ch.
Marek
M
Basler
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D058947:Bacterial Secretion Systems; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014734:Vibrio cholerae / Q000737:chemistry / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems