5JOF

Crystal structure of VRC03 gHVgLV antigen-binding fragment.

Summary for 5JOF

• Entry DOI: 10.2210/pdb5jof/pdb
• Descriptor: VRC03 gHV heavy chain, VRC03 gLV light chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hiv-1, cd4 binding site, neutralizing, antibody development, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 8
• Total formula weight: 188766.37

Authors

Joyce, M.G.,Mascola, J.R.,Kwong, P.D. (deposition date: 2016-05-02, release date: 2016-07-27, Last modification date: 2024-11-20)

Primary citation

Davenport, T.M.,Gorman, J.,Joyce, M.G.,Zhou, T.,Soto, C.,Guttman, M.,Moquin, S.,Yang, Y.,Zhang, B.,Doria-Rose, N.A.,Hu, S.L.,Mascola, J.R.,Kwong, P.D.,Lee, K.K.
Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies.
Structure, 24:1346-1357, 2016

PubMed Abstract: Antibody somatic hypermutation (SHM) and affinity maturation enhance antigen recognition by modifying antibody paratope structure to improve its complementarity with the target epitope. SHM-induced changes in paratope dynamics may also contribute to antibody maturation, but direct evidence of this is limited. Here, we examine two classes of HIV-1 broadly neutralizing antibodies (bNAbs) for SHM-induced changes in structure and dynamics, and delineate the effects of these changes on interactions with the HIV-1 envelope glycoprotein (Env). In combination with new and existing structures of unmutated and affinity matured antibody Fab fragments, we used hydrogen/deuterium exchange with mass spectrometry to directly measure Fab structural dynamics. Changes in antibody structure and dynamics were positioned to improve complementarity with Env, with changes in dynamics primarily observed at the paratope peripheries. We conclude that SHM optimizes paratope complementarity to conserved HIV-1 epitopes and restricts the mobility of paratope-peripheral residues to minimize clashes with variable features on HIV-1 Env.

PubMed: 27477385
DOI: 10.1016/j.str.2016.06.012

Experimental method

X-RAY DIFFRACTION (3.208 Å)