Molecular basis of host-adaptation interactions between influenza virus polymerase PB2 subunit and ANP32A.

Nature Communications
Aldo R Camacho-ZarcoMartin Blackledge

Abstract

Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Adaptive mutants are localised on the C-terminal (627-NLS) domains of the PB2 subunit. In particular, mutation of PB2 residue 627 from E to K rescues polymerase activity in mammalian cells. A host transcription regulator ANP32A, comprising a long C-terminal intrinsically disordered domain (IDD), is responsible for this adaptation. Human ANP32A IDD lacks a 33 residue insertion compared to avian ANP32A, and this deletion restricts avian influenza polymerase activity. We used NMR to determine conformational ensembles of E627 and K627 forms of 627-NLS of PB2 in complex with avian and human ANP32A. Human ANP32A IDD transiently binds to the 627 domain, exploiting multivalency to maximise affinity. E627 interrupts the polyvalency of the interaction, an effect compensated by an avian-unique motif in the IDD. The observed binding mode is maintained in the context of heterotrimeric influenza polymerase, placing ANP32A in the immediate vicinity of known host-adaptive PB2 mutants.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Sep 29, 2004·Journal of Biomolecular NMR·Young-Sang Jung, Markus Zweckstetter
Feb 9, 2006·PLoS Biology·Henry Nicholls
Nov 8, 2006·Protein Science : a Publication of the Protein Society·Joseph A MarshJulie D Forman-Kay
Dec 21, 2006·Journal of Biomolecular NMR·Cesira de ChiaraAnnalisa Pastore
Feb 21, 2007·Nature Structural & Molecular Biology·Franck TarendeauDarren J Hart
Dec 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Andrew Mehle, Jennifer A Doudna
May 27, 2010·Journal of the American Chemical Society·Loïc SalmonMartin Blackledge
Jun 13, 2012·Journal of Biomolecular NMR·Nils-Alexander LakomekAd Bax
Jun 5, 2013·Virus Research·Gülsah GabrielHans-Dieter Klenk
Aug 27, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Patrick T ReillyLishun Wang
Nov 20, 2014·Nature·Alexander PflugStephen Cusack
Oct 2, 2015·Journal of the American Chemical Society·Elise DelaforgeMartin Blackledge
Feb 13, 2016·Cell Host & Microbe·Andrew Mehle
Dec 8, 2016·Biophysical Journal·Martin J FossatCatherine A Royer
Sep 14, 2017·Cell Reports·Patricia Domingues, Benjamin G Hale
Feb 22, 2018·Nature·Alessandro BorgiaBenjamin Schuler
Jun 19, 2018·Molecular Cell·Itziar Serna MartinErvin Fodor
Nov 30, 2018·Nature Reviews. Microbiology·Jason S LongWendy S Barclay
Jun 5, 2019·Nature Structural & Molecular Biology·Tomas KoubaStephen Cusack
Jun 11, 2019·ELife·Steven F Baker, Andrew Mehle
Jun 19, 2019·Nature Microbiology·Qi PengYi Shi
Jun 21, 2019·Journal of Virology·Ecco StallerWendy S Barclay

❮ Previous
Next ❯

Citations

Nov 20, 2020·Nature·Loïc CarriqueJonathan M Grimes
Dec 16, 2020·Biosafety and Health·Yasuha Arai, Yohei Watanabe
Jun 9, 2021·The Biochemical Journal·Kaare TeilumBirthe B Kragelund
Aug 28, 2021·Biomolecules·Estella A NewcombeBirthe B Kragelund
Sep 16, 2021·The Journal of General Virology·Ecco StallerWendy S Barclay
Sep 30, 2020·Cold Spring Harbor Perspectives in Medicine·Ecco Staller, Wendy S Barclay

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
pull-down
electron
X-ray
size-exclusion chromatography

Key Resources (RRID) Mentioned

Addgene_31563

Software Mentioned

Sparky
SSP
Haddock
ASTEROIDS
NMRPipe

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.