View source for 5nuh


==Crystal structure of SIVmac239 Nef bound to an engineered Hck SH3 domain==
<StructureSection load='5nuh' size='340' side='right'caption='[[5nuh]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nuh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NUH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.78&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nuh OCA], [https://pdbe.org/5nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nuh RCSB], [https://www.ebi.ac.uk/pdbsum/5nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nuh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5QGG3_SIV Q5QGG3_SIV] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 A 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.HIV and simian immunodeficiency virus (SIV) Nef proteins both stimulate the clathrin-mediated endocytosis of CD4 but differ in downmodulation of the immune receptor CD3. Here, the authors present the structure of SIV Nef bound to the ExxxLM motif of another Nef molecule, which allows them to propose a model how Nef recognizes these motifs in CD3 and CD4.

Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3.,Manrique S, Sauter D, Horenkamp FA, Lulf S, Yu H, Hotter D, Anand K, Kirchhoff F, Geyer M Nat Commun. 2017 Sep 5;8(1):442. doi: 10.1038/s41467-017-00481-z. PMID:28874665<ref>PMID:28874665</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nuh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein Nef 3D structures|Protein Nef 3D structures]]
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Simian immunodeficiency virus]]
[[Category: Anand K]]
[[Category: Geyer M]]
[[Category: Horenkamp FA]]