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PDBsum entry 3lrs
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protein ligands Protein-protein interface(s) links
Immune system PDB id
3lrs

 

 

 

 

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Contents
Protein chains
220 a.a. *
211 a.a. *
Ligands
NAG ×4
Waters ×389
* Residue conservation analysis
PDB id:
3lrs
Name: Immune system
Title: Structure of pg16, an antibody with broad and potent neutralization of HIV-1
Structure: Pg-16 heavy chain fab. Chain: h, a, c, e. Engineered: yes. Pg-16 light chain fab. Chain: l, b, d, f. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293f. Expression_system_organ: kidney.
Resolution:
2.37Å     R-factor:   0.213     R-free:   0.260
Authors: M.Pancera,P.D.Kwong
Key ref: M.Pancera et al. (2010). Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1. J Virol, 84, 8098-8110. PubMed id: 20538861
Date:
11-Feb-10     Release date:   09-Jun-10    
PROCHECK
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 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 220 a.a.
Protein chains
No UniProt id for this chain
Struc: 211 a.a.
Key:    Secondary structure  CATH domain

 

 
J Virol 84:8098-8110 (2010)
PubMed id: 20538861  
 
 
Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1.
M.Pancera, J.S.McLellan, X.Wu, J.Zhu, A.Changela, S.D.Schmidt, Y.Yang, T.Zhou, S.Phogat, J.R.Mascola, P.D.Kwong.
 
  ABSTRACT  
 
HIV-1 resists neutralization by most antibodies. Two somatically related human antibodies, PG9 and PG16, however, each neutralize 70-80% of circulating HIV-1 isolates. Here we present the structure of the antigen-binding fragment of PG16 in monoclinic and orthorhombic lattices at 2.4 and 4.0 A, respectively, and use a combination of structural analysis, paratope dissection, and neutralization assessment to determine the functional relevance of three unusual PG9/PG16 features: N-linked glycosylation, extensive affinity maturation, and a heavy chain-third complementarity-determining region (CDR H3) that is one of the longest observed in human antibodies. Glycosylation extended off the side of the light chain variable domain and was not required for neutralization. The CDR H3 formed an axe-shaped subdomain, which comprised 42% of the CDR surface, with the axe head looming approximately 20 A above the other combining loops. Comprehensive sets of chimeric swaps between PG9 and PG16 of light chain, heavy chain, and CDR H3 were employed to decipher structure-function relationships. Chimeric swaps generally complemented functionally, with differences in PG9/PG16 neutralization related primarily to residue differences in CDR H3. Meanwhile, chimeric reversions to genomic V-genes showed isolate-dependent effects with affinity maturation playing a significant role in augmenting neutralization breadth (p=0.037) and potency (p<0.0001). The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22982990 D.C.Ekiert, A.K.Kashyap, J.Steel, A.Rubrum, G.Bhabha, R.Khayat, J.H.Lee, M.A.Dillon, R.E.O'Neil, A.M.Faynboym, M.Horowitz, L.Horowitz, A.B.Ward, P.Palese, R.Webby, R.A.Lerner, R.R.Bhatt, and I.A.Wilson (2012).
Cross-neutralization of influenza A viruses mediated by a single antibody loop.
  Nature, 489, 526-532.
PDB codes: 4fnk 4fnl 4fp8 4fqr
21112250 B.F.Haynes, M.A.Moody, H.X.Liao, L.Verkoczy, and G.D.Tomaras (2011).
B cell responses to HIV-1 infection and vaccination: pathways to preventing infection.
  Trends Mol Med, 17, 108-116.  
22113616 J.S.McLellan, M.Pancera, C.Carrico, J.Gorman, J.P.Julien, R.Khayat, R.Louder, R.Pejchal, M.Sastry, K.Dai, S.O'Dell, N.Patel, S.Shahzad-ul-Hussan, Y.Yang, B.Zhang, T.Zhou, J.Zhu, J.C.Boyington, G.Y.Chuang, D.Diwanji, I.Georgiev, Y.D.Kwon, D.Lee, M.K.Louder, S.Moquin, S.D.Schmidt, Z.Y.Yang, M.Bonsignori, J.A.Crump, S.H.Kapiga, N.E.Sam, B.F.Haynes, D.R.Burton, W.C.Koff, L.M.Walker, S.Phogat, R.Wyatt, J.Orwenyo, L.X.Wang, J.Arthos, C.A.Bewley, J.R.Mascola, G.J.Nabel, W.R.Schief, A.B.Ward, I.A.Wilson, and P.D.Kwong (2011).
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
  Nature, 480, 336-343.
PDB codes: 3tcl 3u1s 3u2s 3u36 3u46 3u4b 3u4e
21161615 X.Shen, and G.D.Tomaras (2011).
Alterations of the B-cell response by HIV-1 replication.
  Curr HIV/AIDS Rep, 8, 23-30.  
20829830 J.G.Joyce, and J.ter Meulen (2010).
Pushing the envelope on HIV-1 neutralization.
  Nat Biotechnol, 28, 929-931.  
20616231 T.Zhou, I.Georgiev, X.Wu, Z.Y.Yang, K.Dai, A.Finzi, Y.D.Kwon, J.F.Scheid, W.Shi, L.Xu, Y.Yang, J.Zhu, M.C.Nussenzweig, J.Sodroski, L.Shapiro, G.J.Nabel, J.R.Mascola, and P.D.Kwong (2010).
Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
  Science, 329, 811-817.
PDB code: 3ngb
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 codes are shown on the right.

 

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