1AM9: Human Srebp-1a Bound To Ldl Receptor Promoter

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.
PDB ID: 1AM9Download
MMDB ID: 71564
PDB Deposition Date: 1997/6/25
Updated in MMDB: 2011/06
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1AM9: octameric; determined by author
Molecular Components in 1AM9
Label Count Molecule
Proteins (4 molecules)
Protein (Sterol Regulatory Element Binding Protein 1A)(Gene symbol: SREBF1)
Molecule annotation
Nucleotides(2 molecules)
DNA (5'- D(*tp*tp*gp*cp*ap*gp*tp*gp*gp*gp*gp*tp*gp*ap*tp*cp*t )-3')
Molecule annotation
DNA (5'- D(*cp*ap*tp*gp*ap*gp*ap*tp*cp*ap*cp*cp*cp*cp*ap*cp*t P*gp*cp*ap*a)-3')
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB