text: The active transport of monoamines from the cytosol into storage vesicles operates against a large (>10) concentration gradient.  Secondary active transport is the type of active transport used, meaning that VMAT1 is an antiporter.  This transport is facilitated via proton gradient generated by the protein proton ATPase.  The inward transport of the monoamine is coupled with the efflux of two protons per monoamine.  The first proton is thought to cause a change in VMAT1's conformation, which pushes a high affinity amine binding site, to which the monoamine attaches.  The second proton then causes a second change in the conformation which pulls the monoamine into the vesicle and greatly reduces the affinity of the binding site for amines. A series of tests suggest that His419, located between TMDs X and XI, plays the key role in the first of these conformational changes, and that Asp431, located on TMD XI, does likewise during the second change.