Atomic structure of T6SS reveals interlaced array essential to function.
Type VI secretion systems (T6SSs) are newly identified contractile nanomachines that translocate effector proteins across bacterial membranes. The Francisella pathogenicity island, required for bacterial phagosome escape, intracellular replication, and virulence, was presumed to encode a T6SS-like apparatus. Here, we experimentally confirm the identity of this T6SS and, by cryo electron microscopy (cryoEM), show the structure of its post-contraction sheath at 3.7 Å resolution. We demonstrate the assembly of this T6SS by IglA/IglB and secretion of its putative effector proteins in response to environmental stimuli. The sheath has a quaternary structure with handedness opposite that of contracted sheath of T4 phage tail and is organized in an interlaced two-dimensional array by means of β sheet augmentation. By structure-based mutagenesis, we show that this interlacing is essential to secretion, phagosomal escape, and intracellular replication. Our atomic model of the T6SS will facilitate design of drugs targeting this highly prevalent secretion apparatus.
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Daniel L
DL
Clemens
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; The California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Peng
P
Ge
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bai-Yu
BY
Lee
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: mhorwitz@mednet.ucla.edu.
Marcus A
MA
Horwitz
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; The California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: hong.zhou@ucla.edu.
Z Hong
ZH
Zhou
D001426:Bacterial Proteins / Q000737:chemistry* / Q000648:ultrastructure; D058947:Bacterial Secretion Systems; D017122:Bacteriophage T4 / Q000737:chemistry; D001435:Bacteriophages / Q000737:chemistry; D020285:Cryoelectron Microscopy; D005603:Francisella / Q000648:ultrastructure*; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems