摘要
胶原蛋白是高等动物中最丰富的蛋白质,约占总蛋白质量的1/3.同时,胶原又是重要的生物医用材料,被广泛应用在伤口缝线、软骨缺损填充、骨骼金属植入物镀膜等.目前,在已知的人类28种胶原蛋白中,其中有1/4的胶原构型(7/28)是以异源三聚体的形式存在.由于缺乏对胶原蛋白链间特异性识别与折叠机制的了解,如何通过理性设计来制备清洁来源、纳米尺度可调控的胶原蛋白材料一直是蛋白质工程与生物材料工程交叉领域中的热点和难点问题.迄今为止,在胶原三螺旋中鉴定的最重要的成对相互作用是轴向电荷对,其可以在适当放置的赖氨酸与天冬氨酸或谷氨酸残基之间形成.这些成对氨基酸相互作用将允许制备具有高特异性的异源三聚体螺旋,以及对螺旋结构和稳定性的总体改进控制.此外,对这些相互作用的详细研究将帮助我们修改天然胶原蛋白序列,制造清洁来源、高度可控和成分响应的胶原蛋白生物材料.本综述将总结我们对这种相互作用和其他电荷对相互作用的理解,以及它们如何成功地用于控制胶原三螺旋自组装并探索新的蛋白质设计策略.
As an important biomedical material, collagen has been widely used in wound sutures, cartilage defect filling, and bone metal implant coating. Seven out of the twenty-eight types of natural collagen are heterotrimers comprising three chains with different primary sequences. It is important to understand the intermolecular forces underlying the hetero-specific assembly of natural collagen to modulate material properties in protein engineering and biomaterials engineering. Till date, the most important pairwise interaction identified in the collagen triple helix is the axial charge pair, which can be formed between appropriately placed lysine and aspartate or glutamate residues. These pairwise amino acid interactions enable the preparation of heterotrimeric helices with high specificity, as well as excellent control over helix structure and stability. Further, detailed studies on these interactions will allow the modification of natural collagen sequences to develop clean-sourced, highly controllable, and compositionally responsive collagen biomaterials. This review will summarize our understanding of this interaction and other charged-pair interactions and describe how they have been successfully used to control collagen triple helix self-assembly and explore new protein design strategies.
作者
吕成
强书敏
孙添添
许菲
LU Cheng;QIANG ShuMin;SUN TianTian;XU Fei(School of Biotechnology, Jiangnan University, Wuxi 214122, China)
出处
《中国科学：生命科学》
CSCD
北大核心
2019年第5期615-624,共10页
Scientia Sinica(Vitae)
关键词
胶原蛋白
盐桥相互作用
计算设计
collagen heterotrimer
salt bridge interaction
computational design
