6SKU

Legionella effector AnkX in complex with human Rab1b

Summary for 6SKU

• Entry DOI: 10.2210/pdb6sku/pdb
• Related: 3NKV 4BES
• Descriptor: Phosphocholine transferase AnkX, Ras-related protein Rab-1B, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: disease, post translational modification, crosslink, small g-protein, signaling protein
• Biological source: Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513); More
• Total number of polymer chains: 2
• Total formula weight: 110881.99

Authors

Ernst, S.,Ecker, F.,Kaspers, M.,Ochtrop, P.,Hedberg, C.,Groll, M.,Itzen, A. (deposition date: 2019-08-16, release date: 2020-06-10, Last modification date: 2024-01-24)

Primary citation

Ernst, S.,Ecker, F.,Kaspers, M.S.,Ochtrop, P.,Hedberg, C.,Groll, M.,Itzen, A.
Legionellaeffector AnkX displaces the switch II region for Rab1b phosphocholination.
Sci Adv, 6:eaaz8041-eaaz8041, 2020

PubMed Abstract: The causative agent of Legionnaires disease, , translocates the phosphocholine transferase AnkX during infection and thereby posttranslationally modifies the small guanosine triphosphatase (GTPase) Rab1 with a phosphocholine moiety at S76 using cytidine diphosphate (CDP)-choline as a cosubstrate. The molecular basis for Rab1 binding and enzymatic modification have remained elusive because of lack of structural information of the low-affinity complex with AnkX. We combined thiol-reactive CDP-choline derivatives with recombinantly introduced cysteines in the AnkX active site to covalently capture the heterocomplex. The resulting crystal structure revealed that AnkX induces displacement of important regulatory elements of Rab1 by placing a β sheet into a conserved hydrophobic pocket, thereby permitting phosphocholine transfer to the active and inactive states of the GTPase. Together, the combination of chemical biology and structural analysis reveals the enzymatic mechanism of AnkX and the family of filamentation induced by cyclic adenosine monophosphate (FIC) proteins.

PubMed: 32440549
DOI: 10.1126/sciadv.aaz8041

Experimental method

X-RAY DIFFRACTION (3.2 Å)