Gerstein M, Anderson B F, Norris G E, Baker E N, Lesk A M, Chothia C
MRC Laboratory of Molecular Biology, Cambridge, U.K.
J Mol Biol. 1993 Nov 20;234(2):357-72. doi: 10.1006/jmbi.1993.1592.
Lactoferrin is an iron transport protein. Upon binding iron, the two domains in the N-terminal half of the molecule move together. Previous work has shown that this domain closure involves two hinges. Using the newly refined structure of the open form, the structural mechanism underlying this motion is analyzed here in detail. Upon closure the domains rotate 54 degrees essentially as rigid bodies. The axis of rotation passes through the two beta-strands linking the domains. These strands contain hinges in the sense that three large torsion angle changes are responsible for the bulk of the motion while smaller torsion angle changes in neighboring residues are responsible for the remainder of the motion. The rotation axes of these three torsion angle changes are nearly parallel to the axis of the overall 54 degrees rotation, so the local motion in the hinges can be directly related to the overall motion. A crucial feature of the hinge residues is that they have very few packing constraints on their main-chain atoms. The domains make different packing contacts with each other in the open and closed forms. These contacts form two interdomain interfaces arranged on either side of the hinges. Pivoting about the hinges produces a see-saw motion between the two interfaces. That is, when the domains close down, residues in the interface on one side of the hinges become buried and close-packed and residues on the other side become exposed. The situation is reversed when the domains open up. Lactoferrin provides a particularly clear example of the general features of hinged domain motion. It is compared to other instances of hinged domain closure and contrasted with instances of shear domain closure, where the overall motion is a summation of many small sliding motions between close-packed segments of polypeptide.
乳铁蛋白是一种铁转运蛋白。与铁结合后，分子N端一半的两个结构域会一起移动。先前的研究表明，这种结构域闭合涉及两个铰链。利用新优化的开放形式结构，在此详细分析了这种运动背后的结构机制。闭合时，结构域基本上作为刚体旋转54度。旋转轴穿过连接两个结构域的两条β链。从某种意义上说，这些链包含铰链，因为三个大的扭转角变化负责大部分运动，而相邻残基中较小的扭转角变化负责其余的运动。这三个扭转角变化的旋转轴几乎与整体54度旋转的轴平行，因此铰链中的局部运动可以直接与整体运动相关联。铰链残基的一个关键特征是它们的主链原子几乎没有堆积限制。结构域在开放和闭合形式下彼此形成不同的堆积接触。这些接触形成了位于铰链两侧的两个结构域间界面。围绕铰链旋转会在两个界面之间产生跷跷板运动。也就是说，当结构域闭合时，铰链一侧界面中的残基被掩埋并紧密堆积，而另一侧的残基则暴露出来。当结构域打开时，情况则相反。乳铁蛋白为铰链结构域运动的一般特征提供了一个特别清晰的例子。它与铰链结构域闭合的其他实例进行了比较，并与剪切结构域闭合的实例进行了对比，在剪切结构域闭合中，整体运动是多肽紧密堆积片段之间许多小滑动运动的总和。
