Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

What is it about?

Mutations and MD (molecular dynamics) identified the requirements for proton selectivity of HV1, but could not answer the 2-decade-old question: Does proton selective conduction require protonation/deprotonation of the channel protein, or does it occur via a constrained water-wire? We answer this question by using quantum calculations that include protonation chemistry. The "salt bridge" between Asp112 (in human HV1) and Arg208 occludes the pore with two H bonds. When H3O+ approaches, it breaks these bonds, protonates Asp, and forms a complex AspH0-H2O-Arg+ which can then protonate H2O to complete the cycle. Other ions are excluded.

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