Párraga A, Bellsolell L, Ferré-D'Amaré A R, Burley S K
Laboratories of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA.
Structure. 1998 May 15;6(5):661-72. doi: 10.1016/s0969-2126(98)00067-7.
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').
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.
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.
固醇调节元件结合蛋白（SREBPs）是一种螺旋-环-螺旋转录激活因子，可控制编码胆固醇生物合成/摄取及脂肪酸生物合成所必需蛋白质的基因的表达。与识别对称E盒（5'-CANNTG-3'）的螺旋-环-螺旋蛋白不同，SREBPs在其碱性区域含有酪氨酸而非保守的精氨酸。这种差异使得它们能够识别不对称的固醇调节元件（StRE，5'-ATCACCCAC-3'）。
SREBP-1a与StRE结合的DNA结合部分的2.3埃分辨率共晶体结构显示，其为具有不对称DNA-蛋白质界面的准对称同型二聚体。一个单体利用其他螺旋-环-螺旋蛋白典型的侧链-碱基接触方式结合StRE的E盒半位点（5'-ATCAC-3'）。非E盒半位点（5'-GTGGG-3'）则通过完全不同的蛋白质-DNA接触方式被识别。
尽管SREBPs在结构上与结合E盒的螺旋-环-螺旋蛋白相似，但精氨酸到酪氨酸的取代产生了截然不同的DNA结合特性，这解释了它们如何识别StREs并调节对膜生物合成重要的基因的表达。
