De Wolf E, Gill R, Geddes S, Pitts J, Wollmer A, Grötzinger J
Institut für Biochemie, Rheinisch-Westfälische Technische Hochsclule Aachen, Germany.
Protein Sci. 1996 Nov;5(11):2193-202. doi: 10.1002/pro.5560051106.
Mini insulin-like growth factor 1, an inactive insulin-like growth factor 1 mutant lacking the C region, was studied by 2D NMR spectroscopy. Resonances were assigned for almost all protons of the 57 amino acid residues. The 3D structure of the protein was determined by distance geometry methods. Three helical segments; Ala 8-Cys 18, Gly 42-Phe 49, and Leu 54-Cys 61, were identified, corresponding to those present in wild-type insulin-like growth factor 1 and in single-chain insulin. Their relative orientation, however, was found to be changed. This change is connected with a displacement of the Phe 23-Tyr 24-Phe 25-Asn 26 beta-strand-like segment, i.e., of aromatic side chains known to be important for receptor binding. Thus, deletion of the C region of IGF-1 results in a substantial tertiary structural rearrangement that accounts for the loss of receptor affinity.
微型胰岛素样生长因子1是一种缺乏C区域的无活性胰岛素样生长因子1突变体，通过二维核磁共振光谱对其进行了研究。已对57个氨基酸残基的几乎所有质子进行了共振归属。该蛋白质的三维结构通过距离几何方法确定。鉴定出三个螺旋片段：Ala 8-Cys 18、Gly 42-Phe 49和Leu 54-Cys 61，它们与野生型胰岛素样生长因子1和单链胰岛素中的螺旋片段相对应。然而，发现它们的相对取向发生了变化。这种变化与Phe 23-Tyr 24-Phe 25-Asn 26β链样片段的位移有关，即与已知对受体结合很重要的芳香族侧链的位移有关。因此，IGF-1的C区域缺失导致了大量的三级结构重排，这解释了受体亲和力的丧失。
