4BH8: Crystal Structure Of Germline Antibody 36-65 In Complex With Peptide Gdprpsyishll

Ag recognition by independent primary Abs against a small flexible Ag with overlapping epitopes was analyzed to address the determinants of Ag specificity during the initial encounter. Crystal structures of two distinct dodecapeptide Ags, GDPRPSYISHLL and PPYPAWHAPGNI, in complex with the germline mAb 36-65 were determined and compared with the structures of the same Ags bound to another independent germline mAb, BBE6.12H3. For each peptide Ag, the two germline mAbs recognized overlapping epitopes, but in different topologies. The peptide structures differed, and the two paratopes attained discrete conformations, leading to different surface topologies, in a mode that can be described as adjustable locks and flexible keys. This is in contrast to mature mAbs, in which conformational convergence of different paratopes while binding to a common epitope in a similar conformation has been reported. These results suggest that the primary immune receptor repertoire is highly versatile as compared with its mature counterpart. Germline and mature mAbs adopt distinct mechanisms for recognizing a flexible epitope. Whereas conservation of conformational repertoire is a key characteristic of mature mAbs achieved through affinity maturation, the germline mAbs, at the initial stages of Ag encounter, maintain substantial plasticity, accommodating a broad specificity repertoire.
PDB ID: 4BH8Download
MMDB ID: 119147
PDB Deposition Date: 2013/3/30
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4BH8: trimeric; determined by author and by software (PISA)
Molecular Components in 4BH8
Label Count Molecule
Proteins (3 molecules)
Anti-ars Murine Germline Monoclonal Antibody 36-65
Molecule annotation
Anti-ars Murine Germline Monoclonal Antibody 36-65
Molecule annotation
Dodecapeptide Antigen
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB