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-Structure paper
Title | pH-dependent gating mechanism of the urea channel revealed by cryo-EM. |
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Journal, issue, pages | Sci Adv, Vol. 5, Issue 3, Page eaav8423, Year 2019 |
Publish date | Mar 20, 2019 |
Authors | Yanxiang Cui / Kang Zhou / David Strugatsky / Yi Wen / George Sachs / Z Hong Zhou / Keith Munson / |
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 . ...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. |
External links | Sci Adv / PubMed:30906870 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.7 Å |
Structure data | |
Chemicals | ChemComp-XP4: |
Source |
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Keywords | TRANSPORT PROTEIN / Helicobacter pylori / urea channel / closed state / open state |