Identification of molecular hinge points mediating alternating access in the vesicular monoamine transporter VMAT2.

ABSTRACT: Vesicular monoamine transporter 2 (VMAT2) catalyzes transport of monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons. VMAT2 is a member of the DHA12 family of multidrug transporters that belongs to the major facilitator superfamily (MFS) of secondary transporters. Here we present a homology model of VMAT2, which has the standard MFS fold, that is, with two domains of six transmembrane helices each which are related by twofold pseudosymmetry and whose axis runs normal to the membrane and between the two halves. Demonstration of the essential role of a membrane-embedded glutamate and confirmation of the existence of a hydrogen bond probably involved in proton transport provide experimental evidence that validates some of the predicti

SUBMITTER: Yaffe D 

PROVIDER: S-EPMC3625309 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature