1CR9

CRYSTAL STRUCTURE OF THE ANTI-PRION FAB 3F4

Summary for 1CR9

• Entry DOI: 10.2210/pdb1cr9/pdb
• Descriptor: FAB ANTIBODY LIGHT CHAIN, FAB ANTIBODY HEAVY CHAIN (3 entities in total)
• Functional Keywords: anti-prion antibody, fab 3f4, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47423.72

Authors

Kanyo, Z.F.,Pan, K.M.,Williamson, R.A.,Burton, D.R.,Prusiner, S.B.,Fletterick, R.J.,Cohen, F.E. (deposition date: 1999-08-14, release date: 2000-04-17, Last modification date: 2024-10-16)

Primary citation

Kanyo, Z.F.,Pan, K.M.,Williamson, R.A.,Burton, D.R.,Prusiner, S.B.,Fletterick, R.J.,Cohen, F.E.
Antibody binding defines a structure for an epitope that participates in the PrPC-->PrPSc conformational change.
J.Mol.Biol., 293:855-863, 1999

PubMed Abstract: The X-ray crystallographic structures of the anti-Syrian hamster prion protein (SHaPrP) monoclonal Fab 3F4 alone, as well as the complex with its cognate peptide epitope (SHaPrP 104-113), have been determined to atomic resolution. The conformation of the decapeptide is an Omega-loop. There are substantial alterations in the antibody combining region upon epitope binding. The peptide binds in a U-shaped groove on the Fab surface, with the two specificity determinants, Met109 and Met112, penetrating deeply into separate hydrophobic cavities formed by the heavy and light chain complementarity-determining regions. In addition to the numerous contacts between the Fab and the peptide, two intrapeptide hydrogen bonds are observed, perhaps indicating the structure bound to the Fab exists transiently in solution. This provides the first structural information on a portion of the PrP N-terminal region observed to be flexible in the NMR studies of SHPrP 90-231, SHaPrP 29-231 and mouse PrP 23-231. Antibody characterization of the antigenic surfaces of PrPC and PrPSc identifies this flexible region as a component of the conformational rearrangement that is an essential feature of prion disease.

PubMed: 10543972
DOI: 10.1006/jmbi.1999.3193

Experimental method

X-RAY DIFFRACTION (2 Å)