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-Structure paper
タイトル | Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 112, Issue 38, Page 11947-11952, Year 2015 |
掲載日 | 2015年9月22日 |
著者 | Jean-Philippe Julien / Jeong Hyun Lee / Gabriel Ozorowski / Yuanzi Hua / Alba Torrents de la Peña / Steven W de Taeye / Travis Nieusma / Albert Cupo / Anila Yasmeen / Michael Golabek / Pavel Pugach / P J Klasse / John P Moore / Rogier W Sanders / Andrew B Ward / Ian A Wilson / |
PubMed 要旨 | A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 ...A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 °C and 62.7 °C, respectively) and predominantly native-like, as determined by negative-stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1. |
リンク | Proc Natl Acad Sci U S A / PubMed:26372963 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 9.32 Å |
構造データ | EMDB-3059: |
由来 |
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