4N1E

Structural evidence for antigen receptor evolution

Summary for 4N1E

• Entry DOI: 10.2210/pdb4n1e/pdb
• Related: 4N1C
• Descriptor: immunoglobulin variable light chain domain, Lysozyme C (3 entities in total)
• Functional Keywords: immunoglobulin light chain variable domain, antigen-receptor interaction, ig-fold, immune system-hydrolase complex, immune system/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00698
• Total number of polymer chains: 12
• Total formula weight: 151581.00

Authors

Langley, D.B.,Rouet, R.,Stock, D.,Christ, D. (deposition date: 2013-10-04, release date: 2014-10-29, Last modification date: 2024-11-20)

Primary citation

Rouet, R.,Langley, D.B.,Schofield, P.,Christie, M.,Roome, B.,Porebski, B.T.,Buckle, A.M.,Clifton, B.E.,Jackson, C.J.,Stock, D.,Christ, D.
Structural reconstruction of protein ancestry.
Proc. Natl. Acad. Sci. U.S.A., 114:3897-3902, 2017

PubMed 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.

PubMed: 28356519
DOI: 10.1073/pnas.1613477114

Experimental method

X-RAY DIFFRACTION (2.23 Å)