+Search query
-Structure paper
| Title | Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. |
|---|---|
| Journal, issue, pages | PLoS Pathog, Vol. 11, Issue 1, Page e1004570, Year 2015 |
| Publish date | Jan 8, 2015 |
Authors | Javier Guenaga / Natalia de Val / Karen Tran / Yu Feng / Karen Satchwell / Andrew B Ward / Richard T Wyatt / ![]() |
| PubMed Abstract | The structure of BG505 gp140 SOSIP, a soluble mimic of the native HIV-1 envelope glycoprotein (Env), marks the beginning of new era in Env structure-based immunogen design. Displaying a well-ordered ...The structure of BG505 gp140 SOSIP, a soluble mimic of the native HIV-1 envelope glycoprotein (Env), marks the beginning of new era in Env structure-based immunogen design. Displaying a well-ordered quaternary structure, these subtype A-derived trimers display an excellent antigenic profile, discriminating recognition by broadly neutralizing antibodies (bNAbs) from non-broadly neutralizing antibodies (non-bNAbs), and provide a solid Env-based immunogenic platform starting point. Even with this important advance, obtaining homogeneous well-ordered soluble SOSIP trimers derived from other subtypes remains challenging. Here, we report the "rescue" of homogeneous well-ordered subtype B and C SOSIP trimers from a heterogeneous Env mixture using CD4 binding site-directed (CD4bs) non-bNAbs in a negative-selection purification process. These non-bNAbs recognize the primary receptor CD4bs only on disordered trimers but not on the native Env spike or well-ordered soluble trimers due to steric hindrance. Following negative selection to remove disordered oligomers, we demonstrated recovery of well-ordered, homogeneous trimers by electron microscopy (EM). We obtained 3D EM reconstructions of unliganded trimers, as well as in complex with sCD4, a panel of CD4bs-directed bNAbs, and the cleavage-dependent, trimer-specific bNAb, PGT151. Using bio-layer light interferometry (BLI) we demonstrated that the well-ordered trimers were efficiently recognized by bNAbs and poorly recognized by non-bNAbs, representing soluble mimics of the native viral spike. Biophysical characterization was consistent with the thermostability of a homogeneous species that could be further stabilized by specific bNAbs. This study revealed that Env trimers generate different frequencies of well-ordered versus disordered aberrant trimers even when they are genetically identical. By negatively selecting the native-like well-ordered trimers, we establish a new means to obtain soluble Env mimetics derived from subtypes B and C for expanded use as candidate vaccine immunogens. |
External links | PLoS Pathog / PubMed:25569572 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 18.0 - 24.0 Å |
| Structure data | ![]() EMDB-6189: ![]() EMDB-6190: ![]() EMDB-6191: ![]() EMDB-6192: ![]() EMDB-6193: ![]() EMDB-6194: ![]() EMDB-6195: ![]() EMDB-6196: ![]() EMDB-6197: ![]() EMDB-6198: ![]() EMDB-6199: |
| Source |
|
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors
External links










Simian-Human immunodeficiency virus
Homo sapiens (human)