title: STARD5 specific ligand binding: comparison with STARD1 and STARD4 subfamilies.
abstract: We present herein a review of our recent results on the characterization of the binding sites of STARD1, STARD5 and STARD6 using NMR and other biophysical techniques. Whereas STARD1 and STARD6 bind cholesterol, no cholesterol binding could be detected for STARD5. However, titration of STARD5 with cholic acid and chenodeoxycholic acid led to specific binding. Using perturbation of the (1)H-(15)N-HSQC spectra and the sequence specific NMR assignments, we identified the amino acids in contact with those ligands. The most perturbed residues in presence of ligands are lining the internal cavity of the protein. Interestingly, these residues are not conserved in STARD1 and STARD6 and could therefore be key structural determinants of the specificity of START domains toward their ligands. We highlight three tissues expressing STARD5 that are affected by bile acids.
authors: Département de Biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors: Danny
authors: D
authors: Létourneau
authors: Andrée
authors: A
authors: Lefebvre
authors: Pierre
authors: P
authors: Lavigne
authors: Jean-Guy
authors: JG
authors: LeHoux
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D019826:Cholic Acid / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; C456544:STARD4 protein, human; C456546:STARD5 protein, human; C456545:STARD6 protein, human; D000098682:Steroidogenic Acute Regulatory Protein; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D019826:Cholic Acid