Aggregation-Prone Near-Native Intermediate Formation during Unfolding of a Structurally Similar Nonlenticular 尾纬-Crystallin Domain
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- 作者：V. Rajanikanth ; Shanti Swaroop Srivastava ; Aditya K. Singh ; M. Rajyalakshmi ; Kousik Chandra ; Penmatsa Aravind ; Rajan Sankaranarayanan ; Yogendra Sharma
- 刊名：Biochemistry
- 出版年：2012
- 出版时间：October 30, 2012
- 年：2012
- 卷：51
- 期：43
- 页码：8502-8513
- 全文大小：776K
- 年卷期：v.51,no.43(October 30, 2012)
- ISSN：1520-4995
文摘
The folding and unfolding of structurally similar proteins belonging to a family have long been a focus of investigation of the structure鈥?un)folding relationship. Such studies are yet to reach a consensus about whether structurally similar domains follow common or different unfolding pathways. Members of the 尾纬-crystallin superfamily, which consists of structurally similar proteins with limited sequence similarity from diverse life forms spanning microbes to mammals, form an appropriate model system for exploring this relationship further. We selected a new member, Crybg3_D3, the third 尾纬-crystallin domain of non-lens vertebrate protein Crybg3 from mouse brain. The crystal structure determined at 1.86 脜 demonstrates that the 尾纬-crystallin domain of Crybg3 resembles more closely the lens 尾纬-crystallins than the microbial crystallins do. However, interestingly, this structural cousin follows a quite distinct (un)folding pathway via formation of an intermediate state. The intermediate species is in a nativelike conformation with variation in flexibility and tends to form insoluble aggregates. The individual domains of lens 尾纬-crystallins (and microbial homologues) do not follow such an unfolding pattern. Thus, even the closest members of a subfamily within a superfamily do not necessarily follow similar unfolding paths, suggesting the divergence acquired by these domains, which could be observed only by unfolding. Additionally, this study provides insights into the modifications that this domain has undergone during its recruitment into the non-lens tissues in vertebrates.