Turk D, Guncar G, Turk V
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia.
IUBMB Life. 1999 Jul;48(1):7-12. doi: 10.1080/713803477.
The discovery of a fragment from the p41 form of invariant chain tightly bound to cathepsin L provided the first direct link between MHC class II molecules and the regulation of activity of lysosomal cysteine proteases. We recently determined the crystal structure of this p41 invariant chain fragment in complex with cathepsin L [EMBO J. 18, 793-803 (1999)]. This structure explains the specificity of the observed interactions and actually provides a tool, which can be utilized by means of molecular biology, to explore and understand the specificity of thyroglobulin type I domains and thus allow the design of specific inhibitors of papain-like cysteine proteases. The structure further supports the hypothesis that the thyroglobulin type I and II domains present in various proteins, sometimes in multiple repeats, are regulatory elements of the processing of these proteins by proteolytic cleavage.
发现与组织蛋白酶L紧密结合的恒定链p41形式的一个片段，首次在MHC II类分子与溶酶体半胱氨酸蛋白酶活性调节之间建立了直接联系。我们最近确定了该p41恒定链片段与组织蛋白酶L复合物的晶体结构[《欧洲分子生物学组织杂志》18, 793 - 803(1999)]。该结构解释了所观察到的相互作用的特异性，实际上提供了一种工具，可通过分子生物学手段来探索和理解甲状腺球蛋白I型结构域的特异性，从而有助于设计木瓜蛋白酶样半胱氨酸蛋白酶的特异性抑制剂。该结构进一步支持了这样一种假说，即存在于各种蛋白质中、有时以多个重复形式出现的甲状腺球蛋白I型和II型结构域，是这些蛋白质通过蛋白水解切割进行加工的调节元件。
