Structural basis of oligomerization in the stalk region of dynamin-like MxA
- PMID:20428112
- DOI: 10.1038/nature08972
Structural basis of oligomerization in the stalk region of dynamin-like MxA
Abstract
The interferon-inducible dynamin-like myxovirus resistance protein 1 (MxA; also called MX1) GTPase is a key mediator of cell-autonomous innate immunity against pathogens such as influenza viruses. MxA partially localizes to COPI-positive membranes of the smooth endoplasmic reticulum-Golgi intermediate compartment. At the point of infection, it redistributes to sites of viral replication and promotes missorting of essential viral constituents. It has been proposed that the middle domain and the GTPase effector domain of dynamin-like GTPases constitute a stalk that mediates oligomerization and transmits conformational changes from the G domain to the target structure; however, the molecular architecture of this stalk has remained elusive. Here we report the crystal structure of the stalk of human MxA, which folds into a four-helical bundle. This structure tightly oligomerizes in the crystal in a criss-cross pattern involving three distinct interfaces and one loop. Mutations in each of these interaction sites interfere with native assembly, oligomerization, membrane binding and antiviral activity of MxA. On the basis of these results, we propose a structural model for dynamin oligomerization and stimulated GTP hydrolysis that is consistent with previous structural predictions and has functional implications for all members of the dynamin family.
Similar articles
- Stalk domain of the dynamin-like MxA GTPase protein mediates membrane binding and liposome tubulation via the unstructured L4 loop.von der Malsburg A, Abutbul-Ionita I, Haller O, Kochs G, Danino D.von der Malsburg A, et al.J Biol Chem. 2011 Oct 28;286(43):37858-65. doi: 10.1074/jbc.M111.249037. Epub 2011 Sep 7.J Biol Chem. 2011.PMID:21900240Free PMC article.
- Dynamin-like MxA GTPase: structural insights into oligomerization and implications for antiviral activity.Haller O, Gao S, von der Malsburg A, Daumke O, Kochs G.Haller O, et al.J Biol Chem. 2010 Sep 10;285(37):28419-24. doi: 10.1074/jbc.R110.145839. Epub 2010 Jun 10.J Biol Chem. 2010.PMID:20538602Free PMC article.Review.
- Role of nucleotide binding and GTPase domain dimerization in dynamin-like myxovirus resistance protein A for GTPase activation and antiviral activity.Dick A, Graf L, Olal D, von der Malsburg A, Gao S, Kochs G, Daumke O.Dick A, et al.J Biol Chem. 2015 May 15;290(20):12779-92. doi: 10.1074/jbc.M115.650325. Epub 2015 Mar 31.J Biol Chem. 2015.PMID:25829498Free PMC article.
- Structure of myxovirus resistance protein a reveals intra- and intermolecular domain interactions required for the antiviral function.Gao S, von der Malsburg A, Dick A, Faelber K, Schröder GF, Haller O, Kochs G, Daumke O.Gao S, et al.Immunity. 2011 Oct 28;35(4):514-25. doi: 10.1016/j.immuni.2011.07.012. Epub 2011 Sep 29.Immunity. 2011.PMID:21962493
- Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity.Haller O, Kochs G.Haller O, et al.J Interferon Cytokine Res. 2011 Jan;31(1):79-87. doi: 10.1089/jir.2010.0076. Epub 2010 Dec 19.J Interferon Cytokine Res. 2011.PMID:21166595Review.
Cited by
- An evolutionary perspective on the broad antiviral specificity of MxA.Mitchell PS, Emerman M, Malik HS.Mitchell PS, et al.Curr Opin Microbiol. 2013 Aug;16(4):493-9. doi: 10.1016/j.mib.2013.04.005. Epub 2013 May 28.Curr Opin Microbiol. 2013.PMID:23725670Free PMC article.Review.
- Mechanics of dynamin-mediated membrane fission.Morlot S, Roux A.Morlot S, et al.Annu Rev Biophys. 2013;42:629-49. doi: 10.1146/annurev-biophys-050511-102247.Annu Rev Biophys. 2013.PMID:23541160Free PMC article.Review.
- Contribution of MxB oligomerization to HIV-1 capsid binding and restriction.Buffone C, Schulte B, Opp S, Diaz-Griffero F.Buffone C, et al.J Virol. 2015 Mar;89(6):3285-94. doi: 10.1128/JVI.03730-14. Epub 2015 Jan 7.J Virol. 2015.PMID:25568212Free PMC article.
- Endocytosis and signaling: cell logistics shape the eukaryotic cell plan.Sigismund S, Confalonieri S, Ciliberto A, Polo S, Scita G, Di Fiore PP.Sigismund S, et al.Physiol Rev. 2012 Jan;92(1):273-366. doi: 10.1152/physrev.00005.2011.Physiol Rev. 2012.PMID:22298658Free PMC article.Review.
- Human Antiviral Protein MxA Forms Novel Metastable Membraneless Cytoplasmic Condensates Exhibiting Rapid Reversible Tonicity-Driven Phase Transitions.Davis D, Yuan H, Liang FX, Yang YM, Westley J, Petzold C, Dancel-Manning K, Deng Y, Sall J, Sehgal PB.Davis D, et al.J Virol. 2019 Oct 29;93(22):e01014-19. doi: 10.1128/JVI.01014-19. Print 2019 Nov 15.J Virol. 2019.PMID:31484749Free PMC article.
References
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials