6NSK

CryoEM structure of Helicobacter pylori urea channel in open state.

Summary for 6NSK

• Entry DOI: 10.2210/pdb6nsk/pdb
• EMDB information: 0498 0499
• Descriptor: Acid-activated urea channel, 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE (2 entities in total)
• Functional Keywords: helicobacter pylori, urea channel, open state, transport protein
• Biological source: Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99)
• Total number of polymer chains: 6
• Total formula weight: 145851.53

Authors

Cui, Y.X.,Zhou, K.,Strugatsky, D.,Wen, Y.,Sachs, G.,Munson, K.,Zhou, Z.H. (deposition date: 2019-01-24, release date: 2019-04-03, Last modification date: 2024-03-20)

Primary citation

Cui, Y.,Zhou, K.,Strugatsky, D.,Wen, Y.,Sachs, G.,Zhou, Z.H.,Munson, K.
pH-dependent gating mechanism of theHelicobacter pyloriurea channel revealed by cryo-EM.
Sci Adv, 5:eaav8423-eaav8423, 2019

PubMed Abstract: The urea channel of (UreI) is an ideal drug target for preventing gastric cancer but incomplete understanding of its gating mechanism has hampered development of inhibitors for the eradication of . Here, we present the cryo-EM structures of UreI in closed and open conformations, both at a resolution of 2.7 Å. Our hexameric structures of this small membrane protein (~21 kDa/protomer) resolve its periplasmic loops and carboxyl terminus that close and open the channel, and define a gating mechanism that is pH dependent and requires cooperativity between protomers in the hexamer. Gating is further associated with well-resolved changes in the channel-lining residues that modify the shape and length of the urea pore. Site-specific mutations in the periplasmic domain and urea pore identified key residues important for channel function. Drugs blocking the urea pore based on our structures should lead to a new strategy for eradication.

PubMed: 30906870
DOI: 10.1126/sciadv.aav8423

Experimental method

ELECTRON MICROSCOPY (2.7 Å)