View source for 7lp5


==Structure of Nedd4L WW3 domain==
<StructureSection load='7lp5' size='340' side='right'caption='[[7lp5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lp5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LP5 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEDD4L, KIAA0439, NEDL3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.26 2.3.2.26] </span></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=7lp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lp5 OCA], [https://pdbe.org/7lp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lp5 RCSB], [https://www.ebi.ac.uk/pdbsum/7lp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lp5 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/AMOT_HUMAN AMOT_HUMAN]] Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions.<ref>PMID:11257124</ref> <ref>PMID:16678097</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Like most enveloped viruses, HIV must acquire a lipid membrane as it assembles and buds through the plasma membrane of infected cells to spread infection. Several sets of host cell machinery facilitate this process, including proteins of the endosomal sorting complexes required for transport pathway, which mediates the membrane fission reaction required to complete viral budding, as well as angiomotin (AMOT) and NEDD4L, which bind one another and promote virion membrane envelopment. AMOT and NEDD4L interact through the four NEDD4L WW domains and three different AMOT Pro-Pro-x (any amino acid)-Tyr (PPxY) motifs, but these interactions are not yet well defined. Here, we report that individual AMOT PPxY and NEDD4L WW domains interact with the following general affinity hierarchies: AMOT PPxY1&gt;PPxY2&gt;PPxY3 and NEDD4L WW3&gt;WW2&gt;WW1 approximately WW4. The unusually high-affinity of the AMOT PPxY1-NEDD4L WW3 interaction accounts for most of the AMOT-NEDD4L binding and is critical for stimulating HIV-1 release. Comparative structural, binding, and virological analyses reveal that complementary ionic and hydrophobic contacts on both sides of the WW-PPxY core interaction account for the unusually high affinity of the AMOT PPxY1-NEDD4L WW3 interaction. Taken together, our studies reveal how the first AMOT PPxY1 motif binds the third NEDD4L WW domain to stimulate HIV-1 viral envelopment and promote infectivity.

Interactions between AMOT PPxY motifs and NEDD4L WW domains function in HIV-1 release.,Rheinemann L, Thompson T, Mercenne G, Paine EL, Peterson FC, Volkman BF, Alam SL, Alian A, Sundquist WI J Biol Chem. 2021 Jul 17;297(2):100975. doi: 10.1016/j.jbc.2021.100975. PMID:34284061<ref>PMID:34284061</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lp5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Alam, S L]]
[[Category: Alian, A]]
[[Category: Peterson, F C]]
[[Category: Rheinemann, L]]
[[Category: Sundquist, W I]]
[[Category: Thompson, T]]
[[Category: Volkman, B F]]
[[Category: E3 ubiquitin ligase]]
[[Category: Ligase]]
[[Category: Nedd4l]]
[[Category: Ppxy binding]]
[[Category: Ww domain]]