|
|
|
|
|
|
 START Domain | |
|
|
Structure:
 Both the CSD and BA START domain families share a common topology consisting of a seven stranded core beta sheet centered between a pair of alpha helices at the N-terminus and an alpha helix at the C-terminus. The C-terminal alpha helix is packed tightly against the sheet, consistent with a Helix-Grip type fold. A striking feature of the START domains is the long hydrophobic tunnel expanding throughout the length of the domain. By adopting a structure similar to an incomplete beta barrel, the interior face of the beta sheet forms the bottom and sides of this tunnel. The tunnel is in turn, roofed by the C-terminal helix.
Structure reference: Tsujishita, Y. and Hurley, J.H. (2000) Nat. Struct. Bio 7(5), 408-444. PDB: 1EM2.
| |
|
Domain binding and function:
Present in both plants and animals, the steroidogenic acute regulatory protein (StAR) related lipid transfer (START) domain is a 200-210 amino acid motif initially identified as lipid binding domain. Sequence analysis of START domain-containing proteins have suggested that at least 2 families of START domains exist in eukaryotes including the classical START domain (CSD) and the Birch allergen START domain (BA) families, with the latter specific to plants. The tertiary structure predicts that START domains bind a single liphophilic compound within a long hydrophobic tunnel, with at least two key residues in the tunnel wall (Met 307, Asn311 of MLN64) providing the high degree of substrate specificity observed for these domains. The domain structures of family members suggest that in addition to lipid transport, SMART domain containing proteins play roles in both signaling and regulation of transcription.
| |
|
Examples of Proteins:
| START Domain Proteins |
|
Binding Partners |
| StAR |  |
cholesterol |
| PP-CT | |
phosphotidylcholine |
|
|
|
| |
|
Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
| |
|
|
