PDBsum entry 4z3p

Transport protein

PDB id: 4z3p

Contents

Protein chain

431 a.a.

Ligands

CAC

Metals

_RB

Waters ×1

PDB id:

4z3p

Name:

Transport protein

Title:

Mate transporter clbm in complex with rb+

Structure:

Putative drug/sodium antiporter. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: clbm. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.30Å R-factor: 0.207 R-free: 0.287

Authors:

J.J.Mousa,S.D.Bruner

Key ref:

J.J.Mousa et al. (2016). MATE transport of the E. coli-derived genotoxin colibactin. Nat Microbiol, 1, 15009. PubMed id: 27571755 DOI: 10.1038/nmicrobiol.2015.9

Date:

31-Mar-15 Release date: 13-Jan-16

Protein chain

Q0P7K3  (Q0P7K3_ECOLX) -  Drug/sodium antiporter from Escherichia coli

Seq: 479 a.a.

Struc: 431 a.a.

DOI no: 10.1038/nmicrobiol.2015.9

Nat Microbiol 1:15009 (2016)

PubMed id: 27571755

MATE transport of the E. coli-derived genotoxin colibactin.

J.J.Mousa, Y.Yang, S.Tomkovich, A.Shima, R.C.Newsome, P.Tripathi, E.Oswald, S.D.Bruner, C.Jobin.

ABSTRACT

Various forms of cancer have been linked to the carcinogenic activities of microorganisms(1-3). The virulent gene island polyketide synthase (pks) produces the secondary metabolite colibactin, a genotoxic molecule(s) causing double-stranded DNA breaks(4) and enhanced colorectal cancer development(5,6). Colibactin biosynthesis involves a prodrug resistance strategy where an N-terminal prodrug scaffold (precolibactin) is assembled, transported into the periplasm and cleaved to release the mature product(7-10). Here, we show that ClbM, a multidrug and toxic compound extrusion (MATE) transporter, is a key component involved in colibactin activity and transport. Disruption of clbM attenuated pks+ E. coli-induced DNA damage in vitro and significantly decreased the DNA damage response in gnotobiotic Il10(-/-) mice. Colonization experiments performed in mice or zebrafish animal models indicate that clbM is not implicated in E. coli niche establishment. The X-ray structure of ClbM shows a structural motif common to the recently described MATE family. The 12-transmembrane ClbM is characterized as a cation-coupled antiporter, and residues important to the cation-binding site are identified. Our data identify ClbM as a precolibactin transporter and provide the first structure of a MATE transporter with a defined and specific biological function.