DOMAIN CLOSURE IN LACTOFERRIN - 2 HINGES PRODUCE A SEE-SAW MOTION BETWEEN ALTERNATIVE CLOSE-PACKED INTERFACES

被引:148
作者
GERSTEIN, M
ANDERSON, BF
NORRIS, GE
BAKER, EN
LESK, AM
CHOTHIA, C
机构
[1] UNIV CAMBRIDGE,DEPT CHEM,CAMBRIDGE CB2 1EW,ENGLAND
[2] MASSEY UNIV,DEPT CHEM & BIOCHEM,PALMERSTON NORTH,NEW ZEALAND
[3] UNIV CAMBRIDGE,DEPT HAEMATOL,CAMBRIDGE CB2 2QH,ENGLAND
[4] CAMBRIDGE CTR PROT ENGN,CAMBRIDGE CB2 2QH,ENGLAND
基金
英国惠康基金;
关键词
MACROMOLECULAR STRUCTURE; PROTEIN DYNAMICS; CONFORMATIONAL CHANGE; HELIX SHEAR MOTION; BINDING PROTEINS;
D O I
10.1006/jmbi.1993.1592
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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° essentially as rigid bodies. The axis of rotation passes through the two β-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° 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. © 1993 Academic Press Limited.
引用
收藏
页码:357 / 372
页数:16
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