7lp5

Structure of Nedd4L WW3 domainStructure of Nedd4L WW3 domain

Structural highlights

7lp5 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NEDD4L, KIAA0439, NEDL3 (HUMAN)
Activity:	Transferase, with EC number 2.3.2.26
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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>PPxY2>PPxY3 and NEDD4L WW3>WW2>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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol. 2001 Mar 19;152(6):1247-54. PMID:11257124
↑ Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell. 2006 May 5;125(3):535-48. doi: 10.1016/j.cell.2006.02.045. PMID:16678097 doi:http://dx.doi.org/10.1016/j.cell.2006.02.045
↑ Rheinemann L, Thompson T, Mercenne G, Paine EL, Peterson FC, Volkman BF, Alam SL, Alian A, Sundquist WI. Interactions between AMOT PPxY motifs and NEDD4L WW domains function in HIV-1 release. J Biol Chem. 2021 Jul 17;297(2):100975. doi: 10.1016/j.jbc.2021.100975. PMID:34284061 doi:http://dx.doi.org/10.1016/j.jbc.2021.100975

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OCA

[1] Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L. Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol. 2001 Mar 19;152(6):1247-54. PMID:11257124

[2] Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell. 2006 May 5;125(3):535-48. doi: 10.1016/j.cell.2006.02.045. PMID:16678097 doi:http://dx.doi.org/10.1016/j.cell.2006.02.045

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

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