5oec

Human Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutantHuman Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutant

Structural highlights

5oec is a 2 chain structure with sequence from Homo sapiens and Salmonella enterica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q6EAT3_SALER

Publication Abstract from PubMed

Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2.

The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.,Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A. The protease GtgE from Salmonella exclusively targets inactive Rab GTPases. Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974 doi:http://dx.doi.org/10.1038/s41467-017-02110-1

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Wachtel R, Brauning B, Mader SL, Ecker F, Kaila VRI, Groll M, Itzen A. The protease GtgE from Salmonella exclusively targets inactive Rab GTPases. Nat Commun. 2018 Jan 3;9(1):44. doi: 10.1038/s41467-017-02110-1. PMID:29298974 doi:http://dx.doi.org/10.1038/s41467-017-02110-1

[1]