Molecular architecture of native HIV-1 gp 120 trimers
By Jun Liu, A. Bartesaghi, M. Borgnia, Guillermo Sapiro, S. Subramaniam. Nature, 2008
853 citations recorded by the source corpus.
The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.
Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging, Virology
View Paper: https://www.semanticscholar.org/paper/c9cc00e76ce9ffedaa08d054045eaf2713b206aa
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Citations in the corpus
- Molecular Architecture of the SARS-CoV-2 Virus (2020, background): “The spike population per virus is comparable to HIV (24), but ~5 times less than the Lassa virus (LASV) (25) and 10 times less than the Influenza virus (26).”
- Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “Whether this b-strand inversion at the V1/V2 base in the trimer structures—compared with the CD4-bound (3, 5), antibody-bound (8–10, 35), and unliganded core monomeric crystal structures (2)—can be attributed to oligomer-monomer differences, changes induced by CD4-binding, or the truncation of V1/V2”
- Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9 (2011, neutral): “Localized by electron microscopy to a membrane-distal ‘cap&rsquo”
- Epitope-Independent Purification of Native-Like Envelope Trimers from Diverse HIV-1 Isolates (2016, methodology): “By making it possible to isolate a broad range of NL Env trimers and use them as reagents (e.g., for antigenicity assays, B cell sorting, and structural analyses), we anticipate that it will become possible to investigate the diversity of HIV-1 Env biology and Env-directed immune responses with grea”
- A collaborative framework for 3D alignment and classification of heterogeneous subvolumes in cryo-electron tomography (2010, background): “, 2002) and adopted by many others (Schmid et al., 2006; Foerster et al., 2008; Liu et al., 2008; Xu et al., 2012).”
- Dynamo: a flexible, user-friendly development tool for subtomogram averaging of cryo-EM data in high-performance computing environments. (2012, methodology): “Subtomogram averaging is becoming an increasingly common tool for cryo-ET studies (Al-Amoudi et al., 2007; Beck et al., 2004; Brandt et al., 2009; Briggs et al., 2009; Liu et al., 2008; Medalia et al., 2002; Ortiz et al., 2010).”