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| Title | Maturation cleavage of the murine leukemia virus Env precursor separates the transmembrane subunits to prime it for receptor triggering. |
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| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 109, Issue 20, Page 7735-7740, Year 2012 |
| Publish date | May 15, 2012 |
 Authors | Robin Löving / Shang-Rung Wu / Mathilda Sjöberg / Birgitta Lindqvist / Henrik Garoff /  |
| PubMed Abstract | The Env protein of murine leukemia virus matures by two cleavage events. First, cellular furin separates the receptor binding surface (SU) subunit from the fusion-active transmembrane (TM) subunit ...The Env protein of murine leukemia virus matures by two cleavage events. First, cellular furin separates the receptor binding surface (SU) subunit from the fusion-active transmembrane (TM) subunit and then, in the newly assembled particle, the viral protease removes a 16-residue peptide, the R-peptide from the endodomain of the TM. Both cleavage events are required to prime the Env for receptor-triggered activation. Cryoelectron microscopy (cryo-EM) analyses have shown that the mature Env forms an open cage-like structure composed of three SU-TM complexes, where the TM subunits formed separated Env legs. Here we have studied the structure of the R-peptide precursor Env by cryo-EM. TM cleavage in Moloney murine leukemia virus was inhibited by amprenavir, and the Envs were solubilized in Triton X-100 and isolated by sedimentation in a sucrose gradient. We found that the legs of the R-peptide Env were held together by trimeric interactions at the very bottom of the Env. This suggested that the R-peptide ties the TM legs together and that this prevents the activation of the TM for fusion. The model was supported by further cryo-EM studies using an R-peptide Env mutant that was fusion-competent despite an uncleaved R-peptide. The Env legs of this mutant were found to be separated, like in the mature Env. This shows that it is the TM leg separation, normally caused by R-peptide cleavage, that primes the Env for receptor triggering. |
 External links | Proc Natl Acad Sci U S A / PubMed:22547812 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 21.0 - 22.0 Å |
| Structure data |  EMDB-2065:  EMDB-2066:  EMDB-2067: |
| Source |
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Moloney murine leukemia virus