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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10196124}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10196124 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10196124}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Immunoglubulin]] | | [[Category: Immunoglubulin]] |
| [[Category: Ribonuclease]] | | [[Category: Ribonuclease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:09:38 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:00:24 2008'' |