Structural highlights
5oed is a 2 chain structure with sequence from "bacillus_cholerae-suis"_smith_1894 "bacillus cholerae-suis" smith 1894 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | |
| Related: | 4cym, 4mi7 |
| Gene: | gtgE, IN36_21720, IN69_16745, IN77_18825 ("Bacillus cholerae-suis" Smith 1894), RAB32 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RAB32_HUMAN] Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alto NM, Soderling J, Scott JD. Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics. J Cell Biol. 2002 Aug 19;158(4):659-68. Epub 2002 Aug 19. PMID:12186851 doi:http://dx.doi.org/10.1083/jcb.200204081
- ↑ Seto S, Tsujimura K, Koide Y. Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes. Traffic. 2011 Apr;12(4):407-20. doi: 10.1111/j.1600-0854.2011.01165.x. Epub 2011 , Feb 21. PMID:21255211 doi:10.1111/j.1600-0854.2011.01165.x
- ↑ 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
