1G6V

Complex of the camelid heavy-chain antibody fragment CAB-CA05 with bovine carbonic anhydrase

Summary for 1G6V

• Entry DOI: 10.2210/pdb1g6v/pdb
• Related: 1f2x
• Descriptor: CARBONIC ANHYDRASE, ANTIBODY HEAVY CHAIN, ZINC ION (3 entities in total)
• Functional Keywords: antibody, antigen, complex, immunoglobulin, lyase-immune system complex, lyase/immune system
• Biological source: Camelus dromedarius (Arabian camel); More
• Cellular location: Cytoplasm: P00921
• Total number of polymer chains: 2
• Total formula weight: 42887.44

Authors

Desmyter, A.,Decanniere, K.,Muyldermans, S.,Wyns, L. (deposition date: 2000-11-08, release date: 2000-11-22, Last modification date: 2024-11-13)

Primary citation

Desmyter, A.,Decanniere, K.,Muyldermans, S.,Wyns, L.
Antigen specificity and high affinity binding provided by one single loop of a camel single-domain antibody.
J.Biol.Chem., 276:26285-26290, 2001

PubMed Abstract: Detailed knowledge on antibody-antigen recognition is scarce given the unlimited antibody specificities of which only few have been investigated at an atomic level. We report the crystal structures of an antibody fragment derived from a camel heavy chain antibody against carbonic anhydrase, free and in complex with antigen. Surprisingly, this single-domain antibody interacts with nanomolar affinity with the antigen through its third hypervariable loop (19 amino acids long), providing a flat interacting surface of 620 A(2). For the first time, a single-domain antibody is observed with its first hypervariable loop adopting a type-1 canonical structure. The second hypervariable loop, of unique size due to a somatic mutation, reveals a regular beta-turn. The third hypervariable loop covers the remaining hypervariable loops and the side of the domain that normally interacts with the variable domain of the light chain. Specific amino acid substitutions and reoriented side chains reshape this side of the domain and increase its hydrophilicity. Of interest is the substitution of the conserved Trp-103 by Arg because it opens new perspectives to 'humanize' a camel variable domain of heavy chain of heavy chain antibody (VHH) or to 'camelize' a human or a mouse variable domain of heavy chain of conventional antibody (VH).

PubMed: 11342547
DOI: 10.1074/jbc.M102107200

Experimental method

X-RAY DIFFRACTION (3.5 Å)