9IAE

Structure of a Chimeric Protein Composed of the SNX5 PX Domain and the N-Terminal Region of NCOA7-AS, crystal form I

Summary for 9IAE

• Entry DOI: 10.2210/pdb9iae/pdb
• Descriptor: Sorting nexin-5,Nuclear receptor coactivator 7 (2 entities in total)
• Functional Keywords: snx5, ncoa7-as, chimeric protein, unknown function
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 20698.51

Authors

Arnaud-Arnould, M.,Rebendenne, A.,Tauziet, M.,Urbach, S.,El Koulali, K.,Ricci, E.,Wencker, M.,Moncorge, O.,Blaise, M.,Goujon, C. (deposition date: 2025-02-10, release date: 2026-01-28, Last modification date: 2026-08-19)

Primary citation

Arnaud-Arnould, M.,Rebendenne, A.,Tauziet, M.,Urbach, S.,El Koulali, K.,Ricci, E.P.,Wencker, M.,Moncorge, O.,Blaise, M.,Goujon, C.
SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus.
J.Biol.Chem., :113372-113372, 2026

PubMed Abstract: Interferon-induced antiviral proteins act on the first line of defence against viruses, including influenza A virus (IAV). Among those, the short isoform of Nuclear Receptor Coactivator 7 (NCOA7-AS) has been shown to inhibit IAV entry and more especially the fusion between endosomal and viral membranes. Ectopic expression of NCOA7-AS leads to the increased acidification of the endolysosomal pathway, putatively through NCOA7-AS interaction with the vacuolar ATPase (V-ATPase). However, the precise mechanism of action of NCOA7-AS is not fully understood. Here, we identified the cellular partners of NCOA7-AS by mass spectrometry, including the V-ATPase subunits known to interact with NCOA7-AS. A point mutation disrupting the interaction with the V-ATPase led to loss of antiviral activity against IAV, demonstrating that V-ATPase engagement is required for the antiviral phenotype. Moreover, sorting nexin (SNX) 1/2/5/6 were identified as novel partners of NCOA7-AS. These proteins are involved in retrograde transport of cellular cargoes from endosomes to the trans-Golgi network. We revealed that SNX5/6 interacted directly with NCOA7-AS and were essential for NCOA7-AS antiviral activity against IAV. Interestingly, crystal structures of NCOA7-AS/SNX5 complexes showed that the SNX5-interaction motif in NCOA7-AS was similar to those found in known cargoes of SNX5/6. In addition, we could pinpoint several critical residues that were important for binding and antiviral activity. Collectively, our study identifies novel essential partners for NCOA7-AS antiviral activity and the structural basis for their interaction.

PubMed: 42520939
DOI: 10.1016/j.jbc.2026.113372

Experimental method

X-RAY DIFFRACTION (2.3 Å)