Structural Basis of CD4 Downregulation by HIV-1 Nef
Peter W. Ramirez,
Posted 23 Apr 2020
bioRxiv DOI: 10.1101/2020.04.21.054007
Posted 23 Apr 2020
The HIV-1 Nef protein suppresses multiple immune surveillance mechanisms to promote viral pathogenesis and is an attractive target for the development of novel therapeutics. A key function of Nef is to remove the CD4 receptor from the cell surface by hijacking clathrin- and AP2-dependent endocytosis. However, exactly how Nef does this has been elusive. Here, we present a high-resolution crystal structure that describes the underlying mechanism. An intricate combination of conformational changes occurs in both Nef and AP2 to enable CD4 binding and downregulation. Strikingly, a pocket on Nef previously identified as crucial for recruiting class I MHC is also responsible for recruiting CD4, revealing a potential approach to inhibit two activities of Nef and sensitize the virus to immune clearance. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 271 times
- Download rankings, all-time:
- Site-wide: 61,014 out of 94,912
- In biochemistry: 1,881 out of 3,211
- Year to date:
- Site-wide: 13,888 out of 94,912
- Since beginning of last month:
- Site-wide: 17,263 out of 94,912
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!