Latest results from the lab
HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. The mature Env spikes are the sole antigens on the virion surface. gp120 and gp41 are the receptor recognition and membrane fusion proteins, respectively. The trimeric Env has been the subject of immunogen design for B-cell based HIV vaccine development, and thus its native conformation is of particular importance to the vaccine community. In collaboration with the Bing Chen lab at Boston Children's, we recently reported the high resolution NMR structure of the transmembrane domain (TMD) of HIV-1 gp41 in medium-sized bicelles (diameter of the central bilayer region ~45 A). We found that gp41 TMD forms a trimer in the membrane and its trimerization is important for maintaining the sensitivity of the Env ectodomain (ECD) to trimer-specific, broadly neutralizing antibodies. These observations indicate that the ECD and TMD of HIV-1 Env are conformationally coupled, maintaining the native trimeric state(s) of Env in a cooperative manner. The study is published in Dev & Park et al, Science. 2016, 353(6295):172-5.
Fas/CD95 is an apoptosis-inducing death receptor. Fu et al. determined the transmembrane domain structure of Fas and showed that the trimer assembly, which is mediated by a proline-containing motif, is essential for Fas signaling. The study is published in Fu et al, Molecular Cell. 2016, 61(4):602-13.
©2005 Chou Research Group