Lorand L, Parameswaran K N, Murthy S N
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):537-41. doi: 10.1073/pnas.95.2.537.
The E domain of fibrinogen represents the central region of the protein that, after the removal of fibrinopeptides from the N-termini of its alpha chains by thrombin, orders the noncovalent assembly of fibrin units into a half-staggered array. This structural organization is accomplished purely through noncovalent binding between the E domain of one molecule and the distal D domains of two others. The process of assembly has a physiologically important up-regulatory effect on the next enzymatic phase of blood coagulation, which is the factor XIIIa-catalyzed end-to-end ligation of the gamma chains at the D domains of the protein. Fibrin assembly, as well as the acceleration of the factor XIIIa reaction, could be prevented by Gly-Pro-Arg-Pro, a homologue of the natural sequence of amino acids at the N termini of alpha chains in the E domain. We have now succeeded with a simple double-headed ligand, bis(Gly-Pro-Arg-Pro-amido)polyethylene glycol, in fully replacing the regulatory functions of the large E domains of the native protein.
纤维蛋白原的E结构域代表蛋白质的中心区域，在凝血酶从其α链的N端去除纤维蛋白肽后，它将纤维蛋白单元非共价组装成半交错排列。这种结构组织完全通过一个分子的E结构域与另外两个分子的远端D结构域之间的非共价结合来实现。组装过程对血液凝固的下一个酶促阶段具有重要的生理上调作用，即因子XIIIa催化蛋白质D结构域处γ链的端对端连接。纤维蛋白组装以及因子XIIIa反应的加速可被甘氨酸-脯氨酸-精氨酸-脯氨酸阻止，它是E结构域中α链N端天然氨基酸序列的同系物。我们现在已经成功地用一种简单的双头配体双（甘氨酸-脯氨酸-精氨酸-脯氨酸-酰胺基）聚乙二醇完全取代了天然蛋白质大E结构域的调节功能。
