上海科技大学知识管理系统

Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function. Although it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals, little was known about the transportation mechanism and substrate specificity of spinster. Here, we report a crystal structure of spinster homolog from Hyphomonas neptunium, HnSPNS, in its inward-facing conformation with and without substrate bound. HnSPNS is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices. A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue, R42, which is locked in position by the interactions with conserved residues E129 and R122. Our results suggest that human spinster serves as a transporter translocating negativelycharged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.