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  Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3

Manrique, S., Sauter, D., Horenkamp, F. A., Luelf, S., Yu, H., Hotter, D., et al. (2017). Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3. Nature Communications, 8: 442. doi:10.1038/s41467-017-00481-z.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0001-78D6-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-839F-1
Genre: Journal Article

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https://www.nature.com/articles/s41467-017-00481-z (Publisher version)
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Open Access
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 Creators:
Manrique, Santiago1, 2, Author
Sauter, Daniel2, Author
Horenkamp, Florian A.1, Author
Luelf, Sebastian1, 3, Author
Yu, Hangxing2, Author
Hotter, Dominik2, Author
Anand, Kanchan2, 3, Author
Kirchhoff, Frank2, Author
Geyer, Matthias1, 2, 3, Author
Affiliations:
1Max Planck Institute of Molecular Physiology, Max Planck Society, Otto-Hahn-Str. 11, 44227 Dortmund, DE, ou_1753286              
2External Organizations, ou_persistent22              
3Research Group Physical Biochemistry, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173686              

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 Abstract: Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined. Here, we determine the structure of SIVmac239 Nef bound to the ExxxLM motif of another Nef molecule at 2.5 angstrom resolution. This provides a basis for a structural model, where a hydrophobic crevice in simian immunodeficiency virus (SIV) Nef targets a dileucine motif in CD4 and a tyrosine-based motif in CD3. Introducing key residues into this crevice of HIV-1 Nef enables CD3 binding but an additional N-terminal tyrosine motif is required for internalization. Our resolution of the CD4/Nef/AP2 complex and generation of HIV-1 Nefs capable of CD3 downregulation provide insights into sorting motif interactions and target discrimination of Nef.

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Language(s): eng - English
 Dates: 2017-09-05
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000409394300015
DOI: 10.1038/s41467-017-00481-z
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Title: Nature Communications
  Abbreviation : Nat Commun
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: 442 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723