Linkers in the structural biology of protein-protein interactions

被引:253
作者
Chichili, Vishnu Priyanka Reddy [1 ]
Kumar, Veerendra [1 ]
Sivaraman, J. [1 ]
机构
[1] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore
关键词
protein-protein interactions; X-ray crystallography; linkers; weak binding; MHC CLASS-II; T-CELL-RECEPTOR; X-RAY-STRUCTURE; BOUND SINGLE PEPTIDES; SITU PRODUCT COMPLEX; CRYSTAL-STRUCTURE; HIV-1; PROTEASE; LIGAND-BINDING; CALCINEURIN PEPTIDE; LMO4-LDB1; COMPLEX;
D O I
10.1002/pro.2206
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
Linkers or spacers are short amino acid sequences created in nature to separate multiple domains in a single protein. Most of them are rigid and function to prohibit unwanted interactions between the discrete domains. However, Gly-rich linkers are flexible, connecting various domains in a single protein without interfering with the function of each domain. The advent of recombinant DNA technology made it possible to fuse two interacting partners with the introduction of artificial linkers. Often, independent proteins may not exist as stable or structured proteins until they interact with their binding partner, following which they gain stability and the essential structural elements. Gly-rich linkers have been proven useful for these types of unstable interactions, particularly where the interaction is weak and transient, by creating a covalent link between the proteins to form a stable proteinprotein complex. Gly-rich linkers are also employed to form stable covalently linked dimers, and to connect two independent domains that create a ligand-binding site or recognition sequence. The lengths of linkers vary from 2 to 31 amino acids, optimized for each condition so that the linker does not impose any constraints on the conformation or interactions of the linked partners. Various structures of covalently linked protein complexes have been described using X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy techniques. In this review, we evaluate several structural studies where linkers have been used to improve protein quality, to produce stable proteinprotein complexes, and to obtain protein dimers.
引用
收藏
页码:153 / 167
页数:15
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