2i24: Difference between revisions

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New page: left|200px<br /><applet load="2i24" size="350" color="white" frame="true" align="right" spinBox="true" caption="2i24, resolution 1.35Å" /> '''Crystal structure an...
 
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==Overview==
==Overview==
Sharks express an unusual heavy-chain isotype called IgNAR, whose variable, regions bind antigen as independent soluble domains. To further probe, affinity maturation of the IgNAR response, we structurally characterized, the germline and somatically matured versions of a type II variable (V), region, both in the presence and absence of its antigen, hen egg-white, lysozyme. Despite a disulfide bond linking complementarity determining, regions (CDRs) 1 and 3, both germline and somatically matured V regions, displayed significant structural changes in these CDRs upon complex, formation with antigen. Somatic mutations in the IgNAR V region serve to, increase the number of contacts with antigen, as reflected by a tenfold, increase in affinity, and one of these mutations appears to stabilize the, CDR3 region. In addition, a residue in the HV4 loop plays an important, role in antibody-antigen interaction, consistent with the high rate of, somatic mutations in this non-CDR loop.
Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.


==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Maturation of Shark Single-domain (IgNAR) Antibodies: Evidence for Induced-fit Binding., Stanfield RL, Dooley H, Verdino P, Flajnik MF, Wilson IA, J Mol Biol. 2007 Mar 23;367(2):358-72. Epub 2006 Dec 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17258766 17258766]
Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding., Stanfield RL, Dooley H, Verdino P, Flajnik MF, Wilson IA, J Mol Biol. 2007 Mar 23;367(2):358-72. Epub 2006 Dec 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17258766 17258766]
[[Category: Ginglymostoma cirratum]]
[[Category: Ginglymostoma cirratum]]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Stanfield, R.L.]]
[[Category: Stanfield, R L.]]
[[Category: Wilson, I.A.]]
[[Category: Wilson, I A.]]
[[Category: CL]]
[[Category: CL]]
[[Category: immunoglobulin fold]]
[[Category: immunoglobulin fold]]


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Revision as of 18:48, 21 February 2008

File:2i24.jpg


2i24, resolution 1.35Å

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Crystal structure analysis of the nurse shark New Antigen Receptor PBLA8 variable domain

OverviewOverview

Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.

About this StructureAbout this Structure

2I24 is a Protein complex structure of sequences from Ginglymostoma cirratum with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding., Stanfield RL, Dooley H, Verdino P, Flajnik MF, Wilson IA, J Mol Biol. 2007 Mar 23;367(2):358-72. Epub 2006 Dec 22. PMID:17258766

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