Global structure of HIV-1 neutralizing antibody IgG1 b12 is asymmetric

• Published in: Biochemical and biophysical research communications Vol. 391; no. 1; pp. 947 - 951
• Main Authors: Ashish, Solanki, Ashish K., Boone, Christopher D., Krueger, Joanna K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2010
• Subjects: 60 APPLIED LIFE SCIENCES; ANTIBODIES; Antibodies, Neutralizing - chemistry; CRYSTAL STRUCTURE; Crystallography, X-Ray; DATA ANALYSIS; DIMENSIONS; Guinier approximation; HIV-1 - immunology; HIV-1 neutralizing antibody; Human immunodeficiency virus 1; Humans; Immunoglobulin G - chemistry; Kratky analysis; Molecular modeling; national synchrotron light source; Protein Conformation; SCATTERING; Scattering, Small Angle; SHAPE; SIMULATION; Small-angle X-ray scattering; X-Ray Diffraction; HIV-1; Dmax; RC; RG; Molecular modeling; Guinier approximation; HIV-1 neutralizing antibody; SAXS; Small-angle X-ray scattering; Kratky analysis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.11.170

Human antibody IgG1 b12 is one of the four antibodies known to neutralize a broad range of human immunodeficiency virus-1. The crystal structure of this antibody displayed an asymmetric disposition of the Fab arms relative to its Fc portion. Comparison of structures solved for other IgG1 antibodies led to a notion that crystal packing forces entrapped a “snap-shot” of different conformations accessible to this antibody. To elucidate global structure of this unique antibody, we acquired small-angle X-ray scattering data from its dilute solution. Data analysis indicated that b12 adopts a bilobal globular structure in solution with a radius of gyration and a maximum linear dimension of ∼54 and ∼180Å, respectively. Extreme similarity between its solution and crystal structure concludes that non-flexible, asymmetric shape is an inherent property of this rare antibody.