6EI3

Crystal structure of auto inhibited POT family peptide transporter

Summary for 6EI3

• Entry DOI: 10.2210/pdb6ei3/pdb
• Descriptor: Proton-dependent oligopeptide transporter family protein, (2S)-2,3-DIHYDROXYPROPYL(7Z)-PENTADEC-7-ENOATE (3 entities in total)
• Functional Keywords: pot family, peptide transport, major facilitator superfamily, membrane protein
• Biological source: Xanthomonas campestris
• Total number of polymer chains: 1
• Total formula weight: 61976.30

Authors

Newstead, S.,Brinth, A.,Vogeley, L.,Caffrey, M. (deposition date: 2017-09-17, release date: 2017-11-22, Last modification date: 2024-01-17)

Primary citation

Parker, J.L.,Li, C.,Brinth, A.,Wang, Z.,Vogeley, L.,Solcan, N.,Ledderboge-Vucinic, G.,Swanson, J.M.J.,Caffrey, M.,Voth, G.A.,Newstead, S.
Proton movement and coupling in the POT family of peptide transporters.
Proc. Natl. Acad. Sci. U.S.A., 114:13182-13187, 2017

PubMed Abstract: POT transporters represent an evolutionarily well-conserved family of proton-coupled transport systems in biology. An unusual feature of the family is their ability to couple the transport of chemically diverse ligands to an inwardly directed proton electrochemical gradient. For example, in mammals, fungi, and bacteria they are predominantly peptide transporters, whereas in plants the family has diverged to recognize nitrate, plant defense compounds, and hormones. Although recent structural and biochemical studies have identified conserved sites of proton binding, the mechanism through which transport is coupled to proton movement remains enigmatic. Here we show that different POT transporters operate through distinct proton-coupled mechanisms through changes in the extracellular gate. A high-resolution crystal structure reveals the presence of ordered water molecules within the peptide binding site. Multiscale molecular dynamics simulations confirm proton transport occurs through these waters via Grotthuss shuttling and reveal that proton binding to the extracellular side of the transporter facilitates a reorientation from an inward- to outward-facing state. Together these results demonstrate that within the POT family multiple mechanisms of proton coupling have likely evolved in conjunction with variation of the extracellular gate.

PubMed: 29180426
DOI: 10.1073/pnas.1710727114

Experimental method

X-RAY DIFFRACTION (2.1 Å)