1bzq

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{{STRUCTURE_1bzq| PDB=1bzq | SCENE= }}
{{STRUCTURE_1bzq| PDB=1bzq | SCENE= }}
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'''COMPLEX OF A DROMEDARY SINGLE-DOMAIN VHH ANTIBODY FRAGMENT WITH RNASE A'''
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===COMPLEX OF A DROMEDARY SINGLE-DOMAIN VHH ANTIBODY FRAGMENT WITH RNASE A===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 10196124 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10196124}}
==About this Structure==
==About this Structure==
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[[Category: Immunoglubulin]]
[[Category: Immunoglubulin]]
[[Category: Ribonuclease]]
[[Category: Ribonuclease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:09:38 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:00:24 2008''

Revision as of 17:00, 30 June 2008

Template:STRUCTURE 1bzq

COMPLEX OF A DROMEDARY SINGLE-DOMAIN VHH ANTIBODY FRAGMENT WITH RNASE A

Template:ABSTRACT PUBMED 10196124

About this Structure

1BZQ is a Single protein structure of sequence from Bos taurus and Camelus dromedarius. 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

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