2adi
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Crystal structure of monoclonal anti-CD4 antibody Q425 in complex with Barium
OverviewOverview
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 StructureAbout this Structure
2ADI is a Protein complex structure of sequences from Mus musculus with BA and TRS as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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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