4N1E: Structural evidence for antigen receptor evolution

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.
PDB ID: 4N1EDownload
MMDB ID: 124299
PDB Deposition Date: 2013/10/4
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.23  Å
Source Organism:
Gallus gallus
Similar Structures:
Biological Unit for 4N1E: trimeric; determined by author and by software (PISA)
Molecular Components in 4N1E
Label Count Molecule
Proteins (3 molecules)
Immunoglobulin Variable Light Chain Domain
Molecule annotation
Lysozyme C(Gene symbol: LYZ)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB