2YBR: Crystal Structure Of The Human Derived Single Chain Antibody Fragment (scfv) 9004g In Complex With Cn2 Toxin From The Scorpion Centruroides Noxius Hoffmann

It has previously been reported that several single-chain antibody fragments of human origin (scFv) neutralize the effects of two different scorpion venoms through interactions with the primary toxins of Centruroides noxius Hoffmann (Cn2) and Centruroides suffusus suffusus (Css2). Here we present the crystal structure of the complex formed between one scFv (9004G) and the Cn2 toxin, determined in two crystal forms at 2.5 and 1.9 A resolution. A 15-residue span of the toxin is recognized by the antibody through a cleft formed by residues from five of the complementarity-determining regions of the scFv. Analysis of the interface of the complex reveals three features. First, the epitope of toxin Cn2 overlaps with essential residues for the binding of beta-toxins to its Na(+) channel receptor site. Second, the putative recognition of Css2 involves mainly residues that are present in both Cn2 and Css2 toxins. Finally, the effect on the increase of affinity of previously reported key residues during the maturation process of different scFvs can be inferred from the structure. Taken together, these results provide the structural basis that explain the mechanism of the 9004G neutralizing activity and give insight into the process of directed evolution that gave rise to this family of neutralizing scFvs.
PDB ID: 2YBRDownload
MMDB ID: 89792
PDB Deposition Date: 2011/3/9
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 2.55  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2YBR: trimeric; determined by author and by software (PISA)
Molecular Components in 2YBR
Label Count Molecule
Proteins (3 molecules)
Single Chain Antibody Fragment 9004g
Molecule annotation
Single Chain Antibody Fragment 9004g
Molecule annotation
Beta-mammal Toxin CN2
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB