Voltage-gated proton (Hv1) channels are involved in many physiological processes, such as pH homeostasis and the innate immune response. Zn 2+ is an important physiological inhibitor of Hv1. Sperm cells are quiescent in the male reproductive system due to Zn 2+ inhibition of Hv1 channels, but become active once introduced into the low-Zn 2+ -concentration environment of the female reproductive tract. How Zn 2+ inhibits Hv1 is not completely understood. In this study, we use the voltage clamp fluorometry technique to identify the molecular mechanism of Zn 2+ inhibition of Hv1. We find that Zn 2+ binds to both the activated closed and resting closed states of the Hv1 channel, thereby inhibiting both voltage sensor motion and gate opening. Mutations of some Hv1 residues affect only Zn 2+ inhibition of the voltage sensor motion, whereas mutations of other residues also affect Zn 2+ inhibition of gate opening. These effects are similar in monomeric and dimeric Hv1 channels, suggesting that the Zn 2+ -binding sites are localized within each subunit of the dimeric Hv1. We propose that Zn 2+ binding has two major effects on Hv1: (i) at low concentrations, Zn 2+ binds to one site and prevents the opening conformational change of the pore of Hv1, thereby inhibiting proton conduction; and (ii) at high concentrations, Zn 2+ , in addition, binds to a second site and inhibits the outward movement of the voltage sensor of Hv1. Elucidating the molecular mechanism of how Zn 2+ inhibits Hv1 will further our understanding of Hv1 function and might provide valuable information for future drug development for Hv1 channels.Hv1 | voltage-gated proton channel | Zn2 + | inhibition | molecular model

þ states, pointing to the oblate, spherical, and prolate nature of the consecutive excitations. In addition, they account for the hindrance of the E2 decay from the prolate 0 þ 4 to the spherical 2 þ 1 state, although overestimating its value. This result makes 66 Ni a unique nuclear system, apart from 236;238 U, in which a retarded γ transition from a 0 þ deformed state to a spherical configuration is observed, resembling a shape-isomerlike behavior. DOI: 10.1103/PhysRevLett.118.162502 The concept of potential energy surface (PES) is central in many areas of physics. Usually, the PES displays the potential energy of the system as a function of its geometry. As an example, the PES of a molecule expressed in such coordinates as bond length, valence angles, etc., can be used for finding the minimum energy shape or calculating chemical reaction rates [1]. The idea of potential energy surface in deformation space has also been widely applied to the nucleus at a given spin. For an even-even nucleus at spin 0, the lowest PES minimum corresponds to the ground state (g.s.), while there may exist additional (secondary) minima in which excited 0 þ states can reside: they can be interpreted as ground states of different shapes [2][3][4][5][6]. When a secondary minimum is separated from the main minimum by a high barrier, in the extreme case a long-lived isomer, called shape isomer, can be formed [7]. Shape isomerism at spin zero, so far, has clearly been observed only in actinide nuclei -these isomers decay mainly by fission, and in two cases only, 236 U and 238 U, by very retarded γ-ray branches [8][9][10][11].The existence of shape isomers in lighter systems has been a matter of debate for a long time. Already in the 1980s, a study based on microscopic Hartree-Fock plus BCS calculations, in which a large number of nuclei was surveyed, identified ten isotopes in which a deformed 0 þ state is separated from a spherical structure by a significantly high barrier:66 Ni and 68 Ni, 190;192 Pt, 206;208;210 Os, and 194;196;214

A displacive, 2 nd order structural phase transition at T s =395 K from space group I4 2 m below T s to I 4/m c m above T s has been discovered in the two-dimensional spin dimer compound SrCu 2 (BO 3 ) 2 . The temperature evolution of the structure in both phases has been studied by Xray diffraction and Raman scattering, supplemented by differential scanning calorimetry and SQUID magnetometry. The implications of this transition and of the observed phonon anomalies in Raman scattering for spin-phonon and interlayer coupling in this quantum spin system will be discussed.