Crystal structure of the Mus musculus cholesterol-regulated START protein 4 (StarD4) containing a StAR-related lipid transfer domain.
The x-ray structure of the mouse cholesterol-regulated START protein 4 (StarD4) has been determined at 2.2-A resolution, revealing a compact alpha/beta structure related to the START domain present in the cytoplasmic C-terminal portion of human MLN64. The volume of the putative lipid-binding tunnel was estimated at 847 A(3), which is consistent with the binding of one cholesterol-size lipid molecule. Comparison of the tunnel-lining residues in StarD4 and MLN64-START permitted identification of possible lipid specificity determinants in both molecular tunnels. Homology modeling of related proteins, and comparison of the StarD4 and MLN64-START structures, showed that StarD4 is a member of a large START domain superfamily characterized by the helix-grip fold. Additional mechanistic and evolutionary studies should be facilitated by the availability of a second START domain structure from a distant relative of MLN64.
Romanowski
Michael J
MJ
Laboratories of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. romanom@mail.rockefeller.edu
Soccio
Raymond E
RE
Breslow
Jan L
JL
Burley
Stephen K
SK
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D000098682:Steroidogenic Acute Regulatory Protein
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; C456544:STARD4 protein, human; C499209:Stard4 protein, mouse; D000098682:Steroidogenic Acute Regulatory Protein; D002784:Cholesterol