Rouet, Romain and Langley, David B and Schofield, Peter and Christie, Mary and Roome, Brendan and Porebski, Benjamin T and Buckle, Ashley M and Clifton, Ben E and Jackson, Colin J and Stock, Daniela and Christ, Daniel (2017) Structural reconstruction of protein ancestry. Proceedings of the National Academy of Sciences of the United States of America, 114 (15). pp.3897-3902. ISSN 1091-6490 (OA)
Full text not available from this repository.Abstract
Ancestral protein reconstruction allows the resurrection and characterization of ancient proteins based on computational analyses of sequences of modern-day proteins. Unfortunately, many protein families are highly divergent and not suitable for sequence-based reconstruction approaches. This limitation is exemplified by the antigen receptors of jawed vertebrates (B- and T-cell receptors), heterodimers formed by pairs of Ig domains. These receptors are believed to have evolved from an extinct homodimeric ancestor through a process of gene duplication and diversification; however molecular evidence has so far remained elusive. Here, we use a structural approach and laboratory evolution to reconstruct such molecules and characterize their interaction with antigen. High-resolution crystal structures of reconstructed homodimeric receptors in complex with hen-egg white lysozyme demonstrate how nanomolar affinity binding of asymmetrical antigen is enabled through selective recruitment and structural plasticity within the receptor-binding site. Our results provide structural evidence in support of long-held theories concerning the evolution of antigen receptors, and provide a blueprint for the experimental reconstruction of protein ancestry in the absence of phylogenetic evidence.
| Item Type: | Article |
|---|---|
| Additional Information: | This article is available for free from the publisher's website (click on link above) |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Apr 2017 01:39 |
| Last Modified: | 21 Jan 2018 08:21 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/579 |
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