Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120

A substantial fraction of broadly neutralizing antibodies (bnAbs) in certain HIV-infected donors recognizes glycan-dependent epitopes on HIV-1 gp120. Here, we elucidate how bnAb PGT 135 recognizes its Asn332 glycan-dependent epitope from its crystal structure with gp120, CD4 and Fab 17b at 3.1 Å resolution. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield to access the gp120 protein surface. Electron microscopy reveals PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. The combined structural studies of PGT 135, PGT 128 and 2G12 show this Asn332-dependent epitope is highly accessible and much more extensive than initially appreciated, allowing for multiple binding modes and varied angles of approach, thereby representing a supersite of vulnerability for antibody neutralization

Molecular Composition, Grafting Density and Film Area Affect the Swelling-Induced Au–S Bond Breakage

In previous studies, we reported the first observation of the Au–S bond breakage induced mechanically by the swelling of the surface-tethered weak polyelectrolyte brushes in phosphate buffered saline (PBS), a phenomenon with broad applications in the fields of biosensors and functional surfaces. In this study, three factors, namely the molecular composition, grafting density and film area of the weak polyelectrolyte, carboxylated poly­(oligo­(ethylene glycol) methacrylate-random-2-hydroxyethyl methacrylate) (poly­(OEGMA-r-HEMA)), were studied systematically on how they affected the swelling-induced Au–S bond breakage (ABB). The results showed that, first, the swelling-induced ABB is applicable to a range of molecular compositions and grafting densities; but the critical thickness (<i>T</i>_critical,dry) varied with both of the two factors. An analysis on the swelling ratio further revealed that the difference in the <i>T</i>_critical,dry arose from the difference in the swelling ability. A film needed to swell to ∼250 nm to induce ABB regardless of its composition or structure, thus a higher swelling ratio would lead to a lower <i>T</i>_critical,dry value. Then, the impact of the film area was studied in micrometer- and sub-micrometer-scale brush patterns, which showed that only partial, rather than complete ABB was induced in these microscopic films, resulting in buckling instead of film detaching. These results demonstrated that the ABB is suitable to be used in the design of biosensors, stimulus-responsive materials and mechanochemical devices. Although the >160 μm² required area for uniform ABB hinders the application of ABB in nanolithography, the irreversible buckling provides a facile method of generating rough surfaces