1bzq
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COMPLEX OF A DROMEDARY SINGLE-DOMAIN VHH ANTIBODY FRAGMENT WITH RNASE A
OverviewOverview
BACKGROUND: Camelid serum contains a large fraction of functional, heavy-chain antibodies - homodimers of heavy chains without light chains., The variable domains of these heavy-chain antibodies (VHH) have a long, complementarity determining region 3 (CDR3) loop that compensates for the, absence of the antigen-binding loops of the variable light chains (VL). In, the case of the VHH fragment cAb-Lys3, part of the 24 amino acid long CDR3, loop protrudes from the antigen-binding surface and inserts into the, active-site cleft of its antigen, rendering cAb-Lys3 a competitive enzyme, inhibitor. RESULTS: A dromedary VHH with specificity for bovine RNase A, cAb-RN05, has a short CDR3 loop of 12 amino acids and is not a competitive, enzyme inhibitor. The structure of the cAb-RN05-RNase A complex has been, solved at 2.8 A. The VHH scaffold architecture is close to that of a human, VH (variable heavy chain). The structure of the antigen-binding, hypervariable 1 loop (H1) of both cAb-RN05 and cAb-Lys3 differ from the, known canonical structures; in addition these H1 loops resemble each, other. The CDR3 provides an antigen-binding surface and shields the face, of the domain that interacts with VL in conventional antibodies., CONCLUSIONS: VHHs adopt the common immunoglobulin fold of variable, domains, but the antigen-binding loops deviate from the predicted, canonical structure. We define a new canonical structure for the H1 loop, of immunoglobulins, with cAb-RN05 and cAb-Lys3 as reference structures., This new loop structure might also occur in human or mouse VH domains., Surprisingly, only two loops are involved in antigen recognition; the CDR2, does not participate. Nevertheless, the antigen binding occurs with, nanomolar affinities because of a preferential usage of mainchain atoms, for antigen interaction.
About this StructureAbout this Structure
1BZQ is a Single protein structure of sequence from Bos taurus and Camelus dromedarius with PO4 as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Full crystallographic information is available from OCA.
ReferenceReference
A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops., Decanniere K, Desmyter A, Lauwereys M, Ghahroudi MA, Muyldermans S, Wyns L, Structure. 1999 Apr 15;7(4):361-70. PMID:10196124
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