Summary information and primary citation
- PDB-id
- 1am9; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription-DNA
- Method
- X-ray (2.3 Å)
- Summary
- Human srebp-1a bound to ldl receptor promoter
- Reference
- Parraga A, Bellsolell L, Ferre-D'Amare AR, Burley SK (1998): "Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution." Structure, 6, 661-672. doi: 10.1016/S0969-2126(98)00067-7.
- Abstract
- Background: The sterol regulatory element binding proteins (SREBPs) are helix-loop-helix transcriptional activators that control expression of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. Unlike helix-loop-helix proteins that recognize symmetric E-boxes (5'-CANNTG-3'), the SREBPs have a tyrosine instead of a conserved arginine in their basic regions. This difference allows recognition of an asymmetric sterol regulatory element (StRE, 5'-ATCACCCAC-3').
Results: The 2.3 A resolution co-crystal structure of the DNA-binding portion of SREBP-1a bound to an StRE reveals a quasi-symmetric homodimer with an asymmetric DNA-protein interface. One monomer binds the E-box half site of the StRE (5'-ATCAC-3') using sidechain-base contacts typical of other helix-loop-helix proteins. The non-E-box half site (5'-GTGGG-3') is recognized through entirely different protein-DNA contacts.
Conclusions: Although the SREBPs are structurally similar to the E-box-binding helix-loop-helix proteins, the Arg-->Tyr substitution yields dramatically different DNA-binding properties that explain how they recognize StREs and regulate expression of genes important for membrane biosynthesis.
