3Q1S

HIV-1 neutralizing antibody Z13e1 in complex with epitope display protein

Summary for 3Q1S

• Entry DOI: 10.2210/pdb3q1s/pdb
• Related: 3fn0
• Descriptor: Z13e1 Fab light chain, Z13e1 Fab heavy chain, Interleukin-22, ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, antibody, gp41, immune system-cytokine complex, immune system/cytokine
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: Q9GZX6
• Total number of polymer chains: 3
• Total formula weight: 66175.60

Authors

Stanfield, R.L.,Julien, J.-P.,Pejchal, R.,Gach, J.S.,Zwick, M.B.,Wilson, I.A. (deposition date: 2010-12-17, release date: 2011-11-02, Last modification date: 2024-11-06)

Primary citation

Stanfield, R.L.,Julien, J.P.,Pejchal, R.,Gach, J.S.,Zwick, M.B.,Wilson, I.A.
Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope.
J.Mol.Biol., 414:460-476, 2011

PubMed Abstract: Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K(d) of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

PubMed: 22033480
DOI: 10.1016/j.jmb.2011.10.014

Experimental method

X-RAY DIFFRACTION (2.15 Å)