PDBsum entry 6x1h

Signaling protein

PDB id: 6x1h

Contents

Protein chains

(+ 0 more) 215 a.a.

Metals

_NI

Waters ×1

PDB id:

6x1h

Name:

Signaling protein

Title:

Crystal structure of a guanine nucleotide exchange factor (gef) domain from the orientia tsutsugamushi protein otdub

Structure:

Ulp_protease domain-containing protein. Chain: e, d, b, f, c, a. Engineered: yes

Source:

Orientia tsutsugamushi. Rickettsia tsutsugamushi. Organism_taxid: 334380. Strain: ikeda. Gene: ott_1962. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.91Å R-factor: 0.168 R-free: 0.208

Authors:

C.S.Lim,Y.Xiong

Key ref:

C.Lim et al. (2020). Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi. Proc Natl Acad Sci U S A, 117, 30380-30390. PubMed id: 33184172 DOI: 10.1073/pnas.2018163117

Date:

18-May-20 Release date: 25-Nov-20

Protein chains

B3CVM3  (B3CVM3_ORITI) -  Ubiquitin-like protease family profile domain-containing protein from Orientia tsutsugamushi (strain Ikeda)

Seq: 1368 a.a.

Struc: 215 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1073/pnas.2018163117

Proc Natl Acad Sci U S A 117:30380-30390 (2020)

PubMed id: 33184172

Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi.

C.Lim, J.M.Berk, A.Blaise, J.Bircher, A.J.Koleske, M.Hochstrasser, Y.Xiong.

ABSTRACT

Rho family GTPases regulate an array of cellular processes and are often modulated by pathogens to promote infection. Here, we identify a cryptic guanine nucleotide exchange factor (GEF) domain in the OtDUB protein encoded by the pathogenic bacterium Orientia tsutsugamushi A proteomics-based OtDUB interaction screen identified numerous potential host interactors, including the Rho GTPases Rac1 and Cdc42. We discovered a domain in OtDUB with Rac1/Cdc42 GEF activity (OtDUB_GEF), with higher activity toward Rac1 in vitro. While this GEF bears no obvious sequence similarity to known GEFs, crystal structures of OtDUB_GEF alone (3.0 Å) and complexed with Rac1 (1.7 Å) reveal striking convergent evolution, with a unique topology, on a V-shaped bacterial GEF fold shared with other bacterial GEF domains. Structure-guided mutational analyses identified residues critical for activity and a mechanism for nucleotide displacement. Ectopic expression of OtDUB activates Rac1 preferentially in cells, and expression of the OtDUB_GEF alone alters cell morphology. Cumulatively, this work reveals a bacterial GEF within the multifunctional OtDUB that co-opts host Rac1 signaling to induce changes in cytoskeletal structure.