Conformation of trimeric envelope glycoproteins: the CD4-dependent membrane fusion mechanism of HIV-1.
The HIV-1 envelope glycoproteins are assembled by the trimeric gp120s and gp41s proteins. The gp120 binds sequentially to CD4 and coreceptor for initiating virus entry. Because of noncovalent interaction and heavy glycosylation for envelope glycoproteins, it is highly difficult to determine entire envelope glycoproteins structure now. Such question extremely limits our good understanding of HIV-1 membrane fusion mechanism. Here, a novel and reasonable assembly model of trimeric gp120s and gp41s was proposed based on the conformational dynamics of trimeric gp120-gp41 complex and gp41, respectively. As for gp41, the heptad repeat sequences in the gp41 C-terminal is of enormous flexibility. On the contrary, the heptad repeat sequences in the gp41 N-terminal likely present stable three-helical bundle due to strong nonpolar interaction, and they were predicted to associate three alpha1 helixes from the non-neutralizing face of the gp120 inner domain, which is quite similar to gp41 fusion core structure. Such interaction likely leads to the formation of noncovalent gp120-gp41 complex. In the proposed assembly of trimeric gp120-gp41 complex, three gp120s present not only perfectly complementary and symmetrical distribution around the gp41, but also different flexibility degree in the different structural domains. Thus, the new model can well explain numerous experimental phenomena, present plenty of structural information, elucidate effectively HIV-1 membrane fusion mechanism, and direct to further develop vaccine and novel fusion inhibitors.
Yingliang
Wu
W
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Hong
Yi
Y
Zhijian
Cao
C
Wenxin
Li
L
D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes; D020836:Protein Structure, Quaternary; D053586:Virus Internalization
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D046912:Multiprotein Complexes