1bzq
From Proteopedia
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COMPLEX OF A DROMEDARY SINGLE-DOMAIN VHH ANTIBODY FRAGMENT WITH RNASE A
Overview
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 Structure
1BZQ is a Single protein structure of sequence from Bos taurus and Camelus dromedarius with as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Fri Feb 15 15:33:57 2008
