[START domain-containing proteins: a review of their role in lipid transport and exchange].
Fifteen START domain-containing proteins exist in mammals. On the basis of their structural homology, this family is divided into several sub-families consisting mainly of non-vesicular intracellular lipid carriers. With the exception of the Thioesterase-START subfamily, the other subfamilies are represented among invertebrates. The START domain is always located in the C-terminus of the protein. It is a module of about 210 residues that binds lipids, including sterols. Cholesterol, 25-hydroxycholesterol, phosphatidylcholine, phosphatidylethanolamine and ceramides are ligands for STARD1/STARD3-6, STARD5, STARD2/STARD10, STARD10 and STARD11, respectively. The lipids or sterols bound by the remaining 7 START proteins are unknown. The START domain can be regarded as a lipid-exchange and/or a lipid-sensing domain. The START domain consists in a deep lipid-binding pocket--that shields the hydrophic ligand from the external aqueous environment--covered by a lid formed by a C-terminal alpha helix. Within the same subgroup, such as the sterols-carriers subgroup, different START domains have similar biochemical properties; however, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or misexpression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers.
Alpy
Fabien
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Biologie du Cancer, UPR 6520 CNRS/U964 Inserm/Université Louis Pasteur, BP10142, 67404 Illkirch, CU de Strasbourg, France.
Legueux
François
F
Bianchetti
Laurent
L
Tomasetto
Catherine
C
D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D018387:Codon, Initiator / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000502:physiology*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D011487:Protein Conformation
D002352:Carrier Proteins; D018387:Codon, Initiator; D008055:Lipids; D008074:Lipoproteins; D010743:Phospholipids; D002784:Cholesterol