3BQU

Crystal Structure of the 2F5 Fab'-3H6 Fab Complex

Summary for 3BQU

• Entry DOI: 10.2210/pdb3bqu/pdb
• Descriptor: 2F5 Fab' light chain, 2F5 Fab' heavy chain, 3H6 Fab light chain, ... (5 entities in total)
• Functional Keywords: beta sheet, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 99917.92

Authors

Bryson, S.,Julien, J.-P.,Isenman, D.E.,Kunert, R.,Katinger, H.,Pai, E.F. (deposition date: 2007-12-20, release date: 2008-10-21, Last modification date: 2024-10-16)

Primary citation

Bryson, S.,Julien, J.P.,Isenman, D.E.,Kunert, R.,Katinger, H.,Pai, E.F.
Crystal structure of the complex between the F(ab)' fragment of the cross-neutralizing anti-HIV-1 antibody 2F5 and the F(ab) fragment of its anti-idiotypic antibody 3H6.
J.Mol.Biol., 382:910-919, 2008

PubMed Abstract: The monoclonal antibody 2F5 neutralizes a broad range of human immunodeficiency virus-1 isolates via a conserved epitope on the viral glycoprotein gp41. The conformation of the principal epitope is a type I beta-turn centered on gp41 residues (664)DKW(666); in addition, binding studies indicate that residues N- and C-terminal to this core as well as structurally more distant parts of gp41 also contribute to the interaction. Ab2/3H6 is an anti-idiotypic antibody that inhibits the interaction between 2F5 and gp41 and as such, Ab2/3H6 may, in principle, possess a paratope that mimics the gp41 epitope. To establish the potential of Ab2/3H6 to serve as a guide for the design of vaccine components against human immunodeficiency virus, we investigated the crystal structure of the heterodimeric complex of Ab2/3H6 F(ab) and 2F5 F(ab)'. Ab2/3H6 F(ab) binds to 2F5 F(ab)' via a helix-like protrusion formed by residues (58(H))RYSPSLNTRL(67(H)) of the 2F5 F(ab)' variable domain and proximal to but not overlapping with the gp41 (664)DKW(666) epitope-binding pocket. This defines Ab2/3H6 as an anti-idiotypic antibody of the Ab2gamma class, i.e., an antigen-inhibitable idiotype that does not carry the internal image of the linear primary gp41 (662)ELDKWAS(668) epitope.

PubMed: 18692506
DOI: 10.1016/j.jmb.2008.07.057

Experimental method

X-RAY DIFFRACTION (3 Å)