Darimont B D, Wagner R L, Apriletti J W, Stallcup M R, Kushner P J, Baxter J D, Fletterick R J, Yamamoto K R
Department of Cellular and Molecular Pharmacology, University of California at San Francisco (UCSF), San Francisco, California 94143 USA.
Genes Dev. 1998 Nov 1;12(21):3343-56. doi: 10.1101/gad.12.21.3343.
Combinatorial regulation of transcription implies flexible yet precise assembly of multiprotein regulatory complexes in response to signals. Biochemical and crystallographic analyses revealed that hormone binding leads to the formation of a hydrophobic groove within the ligand binding domain (LBD) of the thyroid hormone receptor that interacts with an LxxLL motif-containing alpha-helix from GRIP1, a coactivator. Residues immediately adjacent to the motif modulate the affinity of the interaction; the motif and the adjacent sequences are employed to different extents in binding to different receptors. Such interactions of amphipathic alpha-helices with hydrophobic grooves define protein interfaces in other regulatory complexes as well. We suggest that these common structural elements impart flexibility to combinatorial regulation, whereas side chains at the interface impart specificity.
转录的组合调控意味着多蛋白调控复合物能根据信号灵活而精确地组装。生化和晶体学分析表明，激素结合导致甲状腺激素受体的配体结合域（LBD）内形成一个疏水凹槽，该凹槽与来自共激活因子GRIP1的含LxxLL基序的α螺旋相互作用。紧邻该基序的残基调节相互作用的亲和力；该基序和相邻序列在与不同受体结合时的使用程度不同。两亲性α螺旋与疏水凹槽的这种相互作用也定义了其他调控复合物中的蛋白质界面。我们认为，这些共同的结构元件赋予组合调控灵活性，而界面处的侧链赋予特异性。
