STRUCTURE AND ASSEMBLY OF COLLAGEN MOLECULES AND FIBRILS

胶原蛋白分子是所有结缔组织的主要结构元素。 组织中 胶原纤维的组织和超微结构各不相同 下一个组织 这项研究的目的是描绘基本的 参与分子原纤维组装的分子事件 过程，并确定调节这些过程的因素。 组装的四个具体方面将被详细检查。 1)元 前α链以适当的化学计量登记， 三股螺旋的形成是由于链接近从内质网释放 网网膜 膜介导的相互作用可以指导这一阶段的 组装件. 无细胞翻译、多核糖体分离和 完成和膜插入研究将用于检查 链条装配机构 2)必须处理间质性前胶原 在稳定的原纤维形成之前，COOH -和NH 2-前肽。 的 NH 2-前肽酶活性是很好理解的，而COOH-前肽酶活性是很好理解的。 尚未分离，其作用部位尚未确定。 证据 COOH-前肽裂解可能与 细胞内分泌过程的晚期和调节 细胞内降解 此事件的处理本地化，以及 其酶学性质有待详细研究。 3)原纤维的形成是一种 由端肽-螺旋受体区域相互作用主导的事件。 的 这种相互作用的明确化学，以及这些化学物质的性质， 分子结构域将通过相互作用研究进行检查， 分离的肽，通过物理研究（CD，FT-IR），并通过相互作用， 构象预测研究。 4)IV型基底膜胶原 形成丝状网络，而不是原纤维，从分子， 最低限度地加工并保留大量的非三联体序列链 片段 晶状体前囊IV型胶原可以通过以下方法获得： 最小程度的降解。 自组装过程将被检查， 热自组装研究和各种电子显微镜技术 包括SLS形成和旋转遮蔽。 从所有这些研究中，我们 应该更好地了解综合和建设的 结缔组织的胶原结构。 我们的研究 分子组装和组织有序化的机制具有最终的 目的是深入了解结缔组织的控制， 疾病及其治疗。

Collagen molecules are the principal structural elements of all connective tissues. Collagen fiber organization and ultrastructure varies from one tissue to the next. The objective of this study is to delineate the basic molecular events which are involved in the molecular fibril assembly processes and to determine the factors which regulate these processes. Four specific aspects of assembly are to be examined in detail. 1) Nascent pro Alpha chains register in the appropriate stoichiometry and initiate triple helix formation as the chains near release from the endoplasmic reticulum membrane. Membrane mediated interactions may guide this phase of assembly. A combination of cell-free translation, polysome isolation and completion, and membrane insertion studies will be used to examine the chain assembly mechanism. 2) Interstitial procollagens must be processed at both COOH - and NH2-propeptides before stable fibrils form. The NH2-propeptidase activity is well understood whereas the COOH- propeptidase has not been isolated and the site of its action not determined. Evidence is accumulating that the COOH-propeptide cleavage might be tied in with late stages of intracellular secretory processing and regulation of intracellular degradation. The processing localization of this event, and its enzymology are to be examined in detail. 3) Fibril formation is an event dominated by telopeptide-helix receptor region interactions. The explicit chemistry of this interaction, and the properties of these molecular domains are to be examined by interaction studies between isolated peptides, by physical studies (CD, FT-IR), and by interaction and conformational predictive studies. 4) Type IV basement membrane collagens form filamentous networks rather than fibrils, from molecules which are minimally processed and retain extensive non-triplet sequence chain segments. Anterior lens-capsule Type IV collagen can be obtained with minimal degradation. The self-assembly process will be examined, by thermal self-assembly studies and various electron microscopic techniques including SLS formation and rotary shadowing. From all these studies we should develop better insights into the synthesis and construction of the collagenous framework of the connective tissues. Our studies of the mechanism of molecular assembly and tissue ordering have the ultimate objective of providing insight into the control of the connective tissue disorders and their treatment.