Abstract:
:Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Liu Q,Acharya P,Dolan MA,Zhang P,Guzzo C,Lu J,Kwon A,Gururani D,Miao H,Bylund T,Chuang GY,Druz A,Zhou T,Rice WJ,Wigge C,Carragher B,Potter CS,Kwong PD,Lusso Pdoi
10.1038/nsmb.3382subject
Has Abstractpub_date
2017-04-01 00:00:00pages
370-378issue
4eissn
1545-9993issn
1545-9985pii
nsmb.3382journal_volume
24pub_type
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