Sundaramoorthy Munirathinam, Meiyappan Muthuraman, Todd Parvin, Hudson Billy G
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA.
J Biol Chem. 2002 Aug 23;277(34):31142-53. doi: 10.1074/jbc.M201740200. Epub 2002 Apr 22.
Type IV collagen, which is present in all metazoan, exists as a family of six homologous alpha(IV) chains, alpha1-alpha6, in mammals. The six chains assemble into three different triple helical protomers and self-associate as three distinct networks. The network underlies all epithelia as a component of basement membranes, which play important roles in cell adhesion, growth, differentiation, tissue repair and molecular ultrafiltration. The specificity of both protomer and network assembly is governed by amino acid sequences of the C-terminal noncollagenous (NC1) domain of each chain. In this study, the structural basis for protomer and network assembly was investigated by determining the crystal structure of the ubiquitous (alpha1)(2).alpha2 NC1 hexamer of bovine lens capsule basement membrane at 2.0 A resolution. The NC1 monomer folds into a novel tertiary structure. The (alpha1)(2).alpha2 trimer is organized through the unique three-dimensional domain swapping interactions. The differences in the primary sequences of the hypervariable region manifest in different secondary structures, which determine the chain specificity at the monomer-monomer interfaces. The trimer-trimer interface is stabilized by the extensive hydrophobic and hydrophilic interactions without a need for disulfide cross-linking.
IV型胶原存在于所有后生动物中，在哺乳动物中它作为由6条同源α(IV)链（α1-α6）组成的一个家族而存在。这6条链组装成3种不同的三螺旋原聚体，并自我缔合成3种不同的网络结构。该网络作为基底膜的一个组成部分存在于所有上皮组织之下，基底膜在细胞黏附、生长、分化、组织修复和分子超滤中发挥着重要作用。原聚体和网络组装的特异性由每条链C端非胶原（NC1）结构域的氨基酸序列决定。在本研究中，通过以2.0 Å分辨率测定牛晶状体囊基底膜中普遍存在的[(α1)2.α2]2 NC1六聚体的晶体结构，研究了原聚体和网络组装的结构基础。NC1单体折叠成一种新颖的三级结构。(α1)2.α2三聚体通过独特的三维结构域交换相互作用而形成。高变区一级序列的差异表现为不同的二级结构，这决定了单体-单体界面处的链特异性。三聚体-三聚体界面通过广泛的疏水和亲水相互作用得以稳定，无需二硫键交联。
