title: The binding site specificity of STARD4 subfamily: Breaking the cholesterol paradigm.
abstract: Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain proteins display diverse expression patterns and cellular localisations. They bind a large variety of lipids and sterols and are involved in lipid metabolism, lipid transfer and cell signalling. The START domain tertiary structure is an α-helix/β-grip fold module of approximately 210 amino acids delimiting an internal cavity forming the binding site. However, the determinants that dictate ligand specificity and the mechanism of ligand entry and exit are ill-defined. Herein, we review and discuss the current knowledge on ligand specificity and binding mechanism of START domains. More specifically, we highlight that the conserved residues of STARD1, STARD3, STARD4, STARD5 and STARD6 START domains binding sterol play an important structural role for the global protein fold, whereas the residues forming the cavity that fits the shape of their respective ligand are divergent, suggesting their participation in ligand specificity. We also explore the potential binding of steroids to STARD6 in the context of ligand selectivity.
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Danny
authors.initials: D
authors.lastname: Létourneau
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Andrée
authors.initials: A
authors.lastname: Lefebvre
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavigne
authors.affiliation: Département de Biochimie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. Electronic address: jean-guy.lehoux@usherbrooke.ca.
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: LeHoux
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001665:Binding Sites; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008322:Mammals / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data
chemical_list: D001647:Bile Acids and Salts; D008024:Ligands; D026901:Membrane Transport Proteins; D002784:Cholesterol
keywords: Binding site; Circular dichroism; STARD5; STARD6; START domain; Sterols