PDBsum entry 1rz8

Immune system

PDB id: 1rz8

Contents

Protein chains

214 a.a. *

228 a.a. *

Waters ×474

* Residue conservation analysis

PDB id:

1rz8

Name:

Immune system

Title:

Crystal structure of human anti-HIV-1 gp120-reactive antibody 17b

Structure:

Fab 17b light chain. Chain: a, c. Engineered: yes. Fab 17b heavy chain. Chain: b, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: human herpesvirus 4. Expression_system_taxid: 10376. Expression_system_cell: immortalized b-cell clone fused with a murine b-cell fusion partner. Murine b-cell fusion partner

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.212 R-free: 0.262

Authors:

C.C.Huang,M.Venturi,S.Majeed,M.J.Moore,S.Phogat,M.-Y.Zhang, D.S.Dimitrov,W.A.Hendrickson,J.Robinson,J.Sodroski,R.Wyatt,H.Choe, M.Farzan,P.D.Kwong

Key ref:

C.C.Huang et al. (2004). Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc Natl Acad Sci U S A, 101, 2706-2711. PubMed id: 14981267 DOI: 10.1073/pnas.0308527100

Date:

24-Dec-03 Release date: 03-Feb-04

Protein chains

No UniProt id for this chain

Struc: 214 a.a.

Protein chains

No UniProt id for this chain

Struc: 228 a.a.

DOI no: 10.1073/pnas.0308527100

Proc Natl Acad Sci U S A 101:2706-2711 (2004)

PubMed id: 14981267

Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120.

C.C.Huang, M.Venturi, S.Majeed, M.J.Moore, S.Phogat, M.Y.Zhang, D.S.Dimitrov, W.A.Hendrickson, J.Robinson, J.Sodroski, R.Wyatt, H.Choe, M.Farzan, P.D.Kwong.

ABSTRACT

The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the HIV-1 coreceptor is protected from humoral recognition by multiple layers of camouflage. Here we present sequence and genomic analyses for 12 antibodies that pierce these defenses and determine the crystal structures of 5. The data reveal mechanisms and atomic-level details for three unusual immune features: posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an alternative molecular mechanism controlling such sulfation, and highly selective V(H)-gene usage. When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition.

Selected figure(s)

Figure 1.
Fig. 1. Structure of the archetype CD4i antibody, 17b. (A) Complexed versus free structure of 17b. The Left two structures show the rerefined YU2 and HXBc2 ternary complexes after superposition of the 17b V[H] framework, with the two complexed Fab 17b in black C^ worm, interacting 17b side chains in green, the N-terminal domain of CD4 in yellow, and the molecular surface of YU2 core gp120 in red, except for the surface within 3.5 Å of 17b, which is blue. In this orientation, the viral membrane would be positioned toward the top of the page. The Right two structures show the two independent copies of free 17b from the P2[1]2[1]2[1] crystals superimposed on the complexed structures. The color and orientation for the complexed structures are the same as in Left, with the free 17b structures shown in blue with magenta interactive residues. The Far Right shows the entire Fab, including the constant portion. Whereas the variable domains are quite similar, considerable differences are seen in the constant portions, especially between the two free structures. (B) Details of gp120-17b interaction at CDR H2 and CDR H3. The electrostatic potential of gp120 is shown at the molecular surface colored blue for electropositive, red for acidic, and white for apolar. The Left two structures show 17b in the same orientation as A. The portion corresponding to the V[H] gene, VH1-69, has been colored green, except for residues altered by somatic mutation, which are colored magenta. The five side chains of the CDR H2 that interact with gp120 are shown: I52, I53, L54, V56, and H58. The Right two structures show an 90° view, adjusted so that the pseudo twofold axes of the Fab are aligned with the edges of the page. In this view, the acidic CDR H3 loop (yellow C^ worm) can be seen reaching up to contact a basic gp120 surface. Side chains of VH1-69 that interact with the CDR H3 loop are shown.

Figure 5.
Fig. 5. Atomic-level details of antibody sulfation. The sulfated tyrosine at position H100 of 412d is shown. Two of the five coordinating ligands (Lys-145 and Gln-147) are from the light chain of a symmetry-related molecule. Electron density (2F[o] - F[c]) is shown at 0.5 .

Figures were selected by an automated process.