9t1m

From Proteopedia

(Difference between revisions)

Current revision

Nuclear export protein/Non-structural protein 2 (NEP/NS2) in complex with artificial alpha Rep protein

Structural highlights

9t1m is a 4 chain structure with sequence from Influenza A virus (A/WSN/1933(H1N1)) and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.33Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0ABF7SXM9_9INFA Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs bound to the protein M1. Since protein M1 is not available in large quantities before late stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the host nucleus until sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enter the host cytoplasm only when associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.[HAMAP-Rule:MF_04067][RuleBase:RU362104] Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs to which the M1 protein is bound. Because the M1 protein is not available in large quantities until the later stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the nucleus before sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enters the cytoplasm only when they have associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.[ARBA:ARBA00024714]

Publication Abstract from PubMed

The influenza virus nuclear export protein (NEP)/non-structural protein 2 (NS2) is a multifunctional protein, involved in viral ribonucleoprotein export from the nucleus, genome replication enhancement, and the adaption of avian influenza to mammals. Despite the growing attention on the importance of NEP in the influenza virus lifecycle and in interspecies transmission, the molecular details of how it performs its various roles are still not fully understood. For the purpose of assisting in structural characterization, a panel of artificial proteins (alphaReps) were selected against influenza virus A NEP(H1N1) by phage display. When complexed with (alphaRep)E4, we were able to crystallize full-length NEP(H1N1), and characterize the NEP-(alphaRep)E4 interface using an integrative native MS-XL-MS strategy, revealing a folded and monomeric NEP conformation. The N- and C-termini of NEP(H1N1) pack together, with the middle linker region resembling a hinge, contrasting a previous structure where NEP is dimeric and elongated. Together these structures demonstrate the plasticity of NEP, a trait which may potentially aid NEP in binding cellular and viral partners. Using isothermal titration calorimetry (ITC) we measured a nanomolar interaction between (alphaRep)E4 and NEP. Similarly, we found that (alphaRep)E4 also binds NEP from human-isolated avian H7N9 and bovine-isolated avian H5N1 influenza viruses. Owing to their high degree of conservation, (alphaRep)E4 likely has the capacity to interact with NEP from numerous influenza A virus strains. Indeed, this, combined with the nanomolar affinity measured between NEP/(alphaRep)E4 could be explored further as a broad-range therapeutic strategy and/or a tool in cellulo to understand NEP function.

Monomeric Structure of Influenza A Virus NEP/NS2 Obtained With an Artificial Protein Highlights Conformational Plasticity.,Stelfox AJ, Bessonne M, Bourhis JM, Erba EB, Albanese P, Compte DP, Nevers Q, Urvoas A, Valerio-Lepiniec M, Minard P, Ruigrok RWH, Crepin T, Delmas B, Ballandras-Colas A J Mol Biol. 2025 Oct 30;437(24):169511. doi: 10.1016/j.jmb.2025.169511. PMID:41175965^[1]

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

References

↑ Stelfox AJ, Bessonne M, Bourhis JM, Erba EB, Albanese P, Compte DP, Nevers Q, Urvoas A, Valerio-Lepiniec M, Minard P, Ruigrok RWH, Crépin T, Delmas B, Ballandras-Colas A. Monomeric Structure of Influenza A Virus NEP/NS2 Obtained With an Artificial Protein Highlights Conformational Plasticity. J Mol Biol. 2025 Oct 30;437(24):169511. PMID:41175965 doi:10.1016/j.jmb.2025.169511

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9t1m"

Categories: Large Structures | Synthetic construct | Ballandras-Colas A | Crepin T | Stelfox AJ

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9t1m is ON HOLD  until Paper Publication
+==Nuclear export protein/Non-structural protein 2 (NEP/NS2) in complex with artificial alpha Rep protein==
+<StructureSection load='9t1m' size='340' side='right'caption='[[9t1m]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9t1m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/WSN/1933(H1N1)) Influenza A virus (A/WSN/1933(H1N1))] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9T1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9T1M 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]] 2.33&#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=9t1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9t1m OCA], [https://pdbe.org/9t1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9t1m RCSB], [https://www.ebi.ac.uk/pdbsum/9t1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9t1m ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0ABF7SXM9_9INFA A0ABF7SXM9_9INFA] Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs bound to the protein M1. Since protein M1 is not available in large quantities before late stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the host nucleus until sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enter the host cytoplasm only when associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.[HAMAP-Rule:MF_04067][RuleBase:RU362104]  Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs to which the M1 protein is bound. Because the M1 protein is not available in large quantities until the later stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the nucleus before sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enters the cytoplasm only when they have associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.[ARBA:ARBA00024714]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The influenza virus nuclear export protein (NEP)/non-structural protein 2 (NS2) is a multifunctional protein, involved in viral ribonucleoprotein export from the nucleus, genome replication enhancement, and the adaption of avian influenza to mammals. Despite the growing attention on the importance of NEP in the influenza virus lifecycle and in interspecies transmission, the molecular details of how it performs its various roles are still not fully understood. For the purpose of assisting in structural characterization, a panel of artificial proteins (alphaReps) were selected against influenza virus A NEP(H1N1) by phage display. When complexed with (alphaRep)E4, we were able to crystallize full-length NEP(H1N1), and characterize the NEP-(alphaRep)E4 interface using an integrative native MS-XL-MS strategy, revealing a folded and monomeric NEP conformation. The N- and C-termini of NEP(H1N1) pack together, with the middle linker region resembling a hinge, contrasting a previous structure where NEP is dimeric and elongated. Together these structures demonstrate the plasticity of NEP, a trait which may potentially aid NEP in binding cellular and viral partners. Using isothermal titration calorimetry (ITC) we measured a nanomolar interaction between (alphaRep)E4 and NEP. Similarly, we found that (alphaRep)E4 also binds NEP from human-isolated avian H7N9 and bovine-isolated avian H5N1 influenza viruses. Owing to their high degree of conservation, (alphaRep)E4 likely has the capacity to interact with NEP from numerous influenza A virus strains. Indeed, this, combined with the nanomolar affinity measured between NEP/(alphaRep)E4 could be explored further as a broad-range therapeutic strategy and/or a tool in cellulo to understand NEP function.
-Authors:
+Monomeric Structure of Influenza A Virus NEP/NS2 Obtained With an Artificial Protein Highlights Conformational Plasticity.,Stelfox AJ, Bessonne M, Bourhis JM, Erba EB, Albanese P, Compte DP, Nevers Q, Urvoas A, Valerio-Lepiniec M, Minard P, Ruigrok RWH, Crepin T, Delmas B, Ballandras-Colas A J Mol Biol. 2025 Oct 30;437(24):169511. doi: 10.1016/j.jmb.2025.169511. PMID:41175965<ref>PMID:41175965</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9t1m" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Ballandras-Colas A]]
+[[Category: Crepin T]]
+[[Category: Stelfox AJ]]

9t1m

From Proteopedia

Current revision

Nuclear export protein/Non-structural protein 2 (NEP/NS2) in complex with artificial alpha Rep protein

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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