PDBsum entry 2adj

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protein metals Protein-protein interface(s) links
Immune system PDB id
Protein chains
211 a.a. *
214 a.a. *
Waters ×30
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of monoclonal anti-cd4 antibody q425 in complex with calcium
Structure: Q425 fab light chain. Chain: a. Q425 fab heavy chain. Chain: b
Source: Mus musculus. House mouse. Organism_taxid: 10090. Other_details: hydridoma. Other_details: hydridoma
Biol. unit: Dimer (from PQS)
2.90Å     R-factor:   0.213     R-free:   0.300
Authors: T.Zhou,D.H.Hamer,W.A.Hendrickson,Q.J.Sattentau,P.D.Kwong
Key ref:
T.Zhou et al. (2005). Interfacial metal and antibody recognition. Proc Natl Acad Sci U S A, 102, 14575-14580. PubMed id: 16195378 DOI: 10.1073/pnas.0507267102
20-Jul-05     Release date:   20-Sep-05    
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Protein chain
Q58EU4  (Q58EU4_MOUSE) - 
Protein chain
No UniProt id for this chain
Struc: 214 a.a.
Key:    Secondary structure  CATH domain


DOI no: 10.1073/pnas.0507267102 Proc Natl Acad Sci U S A 102:14575-14580 (2005)
PubMed id: 16195378  
Interfacial metal and antibody recognition.
T.Zhou, D.H.Hamer, W.A.Hendrickson, Q.J.Sattentau, P.D.Kwong.
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.
  Selected figure(s)  
Figure 4.
Fig. 4. Structure of Fab Q425. (A) Overall structure. The Q425:Ba^2+ complex is shown in ribbon representation, with Ba^2+ ion in red, heavy chain in orange, and light chain in blue. Contoured in green at 6 is the rigid-body difference Fourier (Ba^2+ vs. EDTA; see details in Materials and Methods), marking the position of the Ba^2+ ion. (B) Q425:Ca^2+ structure, showing details of the Ca^2+ binding site. A close-up of the Q425-calcium binding site is shown in an orientation related to A by a 90° rotation around a horizontal axis. The Ca^2+ ion is colored purple, oxygen atoms are colored red, nitrogen atoms are in dark blue, carbon atoms of the heavy chain are in yellow, and carbon atoms of the light chain are in blue. Coordinating ligands are side-chain oxygens from Asn (residue 100a from the CDR H3), Asp (residue 32 from the CDR L1), and Glu (residue 50 from the CDR L2), as well as the backbone carbonyl of residue 92 (in the CDR L3). Ligand distances are shown in Å. (C) Q425:EDTA structure, showing details of the same site shown in B but in the presence of 10 mM EDTA.
Figure 5.
Fig. 5. Calcium dependence of other Q425-like Abs binding to CD4. CD4 was immobilized on a CM5 chip, and the binding of Q425, Q428, and Q4116 IgG was tested. Sensorgrams are shown for Q425, Q428, and Q4116 in the presence of 2.5 mM Ca^2+ and also in the presence of 1 mM EDTA. IgG (144 nM) was passed over the chip starting at 80 s and allowed to associate for 170 s, with the dissociation followed for 5 min.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19815502 J.M.Wojciak, N.Zhu, K.T.Schuerenberg, K.Moreno, W.S.Shestowsky, M.Hiraiwa, R.Sabbadini, and T.Huxford (2009).
The crystal structure of sphingosine-1-phosphate in complex with a Fab fragment reveals metal bridging of an antibody and its antigen.
  Proc Natl Acad Sci U S A, 106, 17717-17722.
PDB code: 3i9g
17598813 S.Phogat, R.T.Wyatt, and G.B.Karlsson Hedestam (2007).
Inhibition of HIV-1 entry by antibodies: potential viral and cellular targets.
  J Intern Med, 262, 26-43.  
17118134 A.Kel, N.Voss, R.Jauregui, O.Kel-Margoulis, and E.Wingender (2006).
Beyond microarrays: Finding key transcription factors controlling signal transduction pathways.
  BMC Bioinformatics, 7, S13.  
17254297 H.H.Lin, L.Y.Han, H.L.Zhang, C.J.Zheng, B.Xie, Z.W.Cao, and Y.Z.Chen (2006).
Prediction of the functional class of metal-binding proteins from sequence derived physicochemical properties by support vector machine approach.
  BMC Bioinformatics, 7, S13.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.