Tsilibary E C, Charonis A S, Reger L A, Wohlhueter R M, Furcht L T
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
J Biol Chem. 1988 Mar 25;263(9):4302-8.
Type IV collagen has the ability to self-assemble by amino end, carboxyl end, and lateral associations to complex network-like structures which can be visualized by rotary shadowing. The main noncollagenous NC1 domain which is located at the carboxyl end of type IV collagen molecules binds to itself to form dimers and also binds along the length of type IV collagen. The latter binding initiates lateral assembly. Following in vitro nonenzymatic glucosylation of the isolated NC1 domain, binding to the helix-rich domain of type IV collagen was impaired. In turbidity experiments, the nonenzymatically glucosylated NC1 domain minimally suppressed the development of turbidity of collagen solutions when compared to control NC1 domain. In rotary shadowing experiments nonenzymatically glucosylated NC1 domain did not significantly inhibit lateral associations or networks formed by type IV collagen, whereas control NC1 domain caused a drastic decrease in laterally assembled structures. These data suggest that nonenzymatic glucosylation of the NC1 domain may interfere with normal assembly of type IV collagen in diabetes mellitus and may be related to abnormal functions of basement membranes in this pathological condition.
IV型胶原能够通过氨基端、羧基端以及侧向缔合自组装成复杂的网络状结构，这种结构可通过旋转投影观察到。位于IV型胶原分子羧基端的主要非胶原NC1结构域自身结合形成二聚体，并且还沿着IV型胶原的长度结合。后者的结合引发侧向组装。在体外对分离的NC1结构域进行非酶糖基化后，其与IV型胶原富含螺旋的结构域的结合受到损害。在浊度实验中，与对照NC1结构域相比，非酶糖基化的NC1结构域对胶原溶液浊度的发展抑制作用最小。在旋转投影实验中，非酶糖基化的NC1结构域并未显著抑制IV型胶原形成的侧向缔合或网络，而对照NC1结构域则导致侧向组装结构急剧减少。这些数据表明，NC1结构域的非酶糖基化可能会干扰糖尿病中IV型胶原的正常组装，并且可能与这种病理状态下基底膜的异常功能有关。
