The x-ray structure of the mouse cholesterol-regulated START protein 4 (StarD4) has been determined at 2.2-Å resolution, revealing a compact α/β 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 Å3, 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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - May 14 2002|
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