Crystal structure of Legionella DotD: insights into the relationship between type IVB and type II/III secretion systems.
The Dot/Icm type IVB secretion system (T4BSS) is a pivotal determinant of Legionella pneumophila pathogenesis. L. pneumophila translocate more than 100 effector proteins into host cytoplasm using Dot/Icm T4BSS, modulating host cellular functions to establish a replicative niche within host cells. The T4BSS core complex spanning the inner and outer membranes is thought to be made up of at least five proteins: DotC, DotD, DotF, DotG and DotH. DotH is the outer membrane protein; its targeting depends on lipoproteins DotC and DotD. However, the core complex structure and assembly mechanism are still unknown. Here, we report the crystal structure of DotD at 2.0 Å resolution. The structure of DotD is distinct from that of VirB7, the outer membrane lipoprotein of the type IVA secretion system. In contrast, the C-terminal domain of DotD is remarkably similar to the N-terminal subdomain of secretins, the integral outer membrane proteins that form substrate conduits for the type II and the type III secretion systems (T2SS and T3SS). A short β-segment in the otherwise disordered N-terminal region, located on the hydrophobic cleft of the C-terminal domain, is essential for outer membrane targeting of DotH and Dot/Icm T4BSS core complex formation. These findings uncover an intriguing link between T4BSS and T2SS/T3SS.
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Noboru
N
Nakano
Tomoko
T
Kubori
Miki
M
Kinoshita
Katsumi
K
Imada
Hiroki
H
Nagai
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000502:physiology*; D003461:Crystallography; D016952:Legionella pneumophila / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012633:Secretin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D008565:Membrane Proteins; D012633:Secretin