2adi
From Proteopedia
(New page: 200px<br /> <applet load="2adi" size="450" color="white" frame="true" align="right" spinBox="true" caption="2adi, resolution 2.80Å" /> '''Crystal structure o...) |
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| - | [[Image:2adi.gif|left|200px]]<br /> | + | [[Image:2adi.gif|left|200px]]<br /><applet load="2adi" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2adi" size=" | + | |
caption="2adi, resolution 2.80Å" /> | caption="2adi, resolution 2.80Å" /> | ||
'''Crystal structure of monoclonal anti-CD4 antibody Q425 in complex with Barium'''<br /> | '''Crystal structure of monoclonal anti-CD4 antibody Q425 in complex with Barium'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The unique ligation properties of metal ions are widely exploited by | + | The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subsequent steps required for viral entry. Here, we use surface-plasmon resonance to show that Q425 requires calcium for recognition of CD4. Specifically, Q425 binding of calcium resulted in a 55,000-fold enhancement in affinity for CD4. X-ray crystallographic analyses of Q425 in the presence of Ca(2+), Ba(2+), or EDTA revealed an exposed metal-binding site, partially coordinated by five atoms contributed from four antibody complementarity-determining regions. The results suggest that Q425 recognition of CD4 involves direct ligation of antigen by the Q425-held calcium, with calcium binding each ligating atom of CD4 with approximately 1.5 kcal/mol of binding energy. This energetic contribution, which is greater than that from a typical protein atom, demonstrates how interfacial metal ligation can play a unique role in antigen recognition. |
==About this Structure== | ==About this Structure== | ||
| - | 2ADI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with BA and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2ADI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=BA:'>BA</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ADI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hamer, D | + | [[Category: Hamer, D H.]] |
| - | [[Category: Hendrickson, W | + | [[Category: Hendrickson, W A.]] |
| - | [[Category: Kwong, P | + | [[Category: Kwong, P D.]] |
| - | [[Category: Sattentau, Q | + | [[Category: Sattentau, Q J.]] |
[[Category: Zhou, T.]] | [[Category: Zhou, T.]] | ||
[[Category: BA]] | [[Category: BA]] | ||
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[[Category: interfacial metal]] | [[Category: interfacial metal]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:18 2008'' |
Revision as of 14:26, 21 February 2008
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Crystal structure of monoclonal anti-CD4 antibody Q425 in complex with Barium
Overview
The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subsequent steps required for viral entry. Here, we use surface-plasmon resonance to show that Q425 requires calcium for recognition of CD4. Specifically, Q425 binding of calcium resulted in a 55,000-fold enhancement in affinity for CD4. X-ray crystallographic analyses of Q425 in the presence of Ca(2+), Ba(2+), or EDTA revealed an exposed metal-binding site, partially coordinated by five atoms contributed from four antibody complementarity-determining regions. The results suggest that Q425 recognition of CD4 involves direct ligation of antigen by the Q425-held calcium, with calcium binding each ligating atom of CD4 with approximately 1.5 kcal/mol of binding energy. This energetic contribution, which is greater than that from a typical protein atom, demonstrates how interfacial metal ligation can play a unique role in antigen recognition.
About this Structure
2ADI is a Protein complex structure of sequences from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Interfacial metal and antibody recognition., Zhou T, Hamer DH, Hendrickson WA, Sattentau QJ, Kwong PD, Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14575-80. Epub 2005 Sep 29. PMID:16195378
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