4Z3P

MATE transporter ClbM in complex with Rb+

Summary for 4Z3P

• Entry DOI: 10.2210/pdb4z3p/pdb
• Related: 4Z3N
• Descriptor: Putative drug/sodium antiporter, RUBIDIUM ION, CACODYLATE ION, ... (4 entities in total)
• Functional Keywords: transporter, transport protein
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 55487.27

Authors

Mousa, J.J.,Bruner, S.D. (deposition date: 2015-03-31, release date: 2016-01-13, Last modification date: 2023-09-27)

Primary citation

Mousa, J.J.,Yang, Y.,Tomkovich, S.,Shima, A.,Newsome, R.C.,Tripathi, P.,Oswald, E.,Bruner, S.D.,Jobin, C.
MATE transport of the E. coli-derived genotoxin colibactin.
Nat Microbiol, 1:15009-15009, 2016

PubMed 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.

PubMed: 27571755
DOI: 10.1038/nmicrobiol.2015.9

Experimental method

X-RAY DIFFRACTION (3.3 Å)