| Structural highlights
Function
[MX1_HUMAN] Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses. Its target viruses include negative-stranded RNA viruses and HBV through binding and inactivation of their ribonucleocapsid. May also antagonize reoviridae and asfarviridae replication. Inhibits thogoto virus (THOV) replication by preventing the nuclear import of viral nucleocapsids. Inhibits La Crosse virus (LACV) replication by sequestering viral nucleoprotein in perinuclear complexes, preventing genome amplification, budding, and egress. Inhibits influenza A virus (IAV) replication by decreasing or delaying NP synthesis and by blocking endocytic traffic of incoming virus particles. Enhances ER stress-mediated cell death after influenza virus infection. May regulate the calcium channel activity of TRPCs.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis of oligomerization in the stalk region of dynamin-like MxA.,Gao S, von der Malsburg A, Paeschke S, Behlke J, Haller O, Kochs G, Daumke O Nature. 2010 May 27;465(7297):502-6. Epub 2010 Apr 28. PMID:20428112[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ku CC, Che XB, Reichelt M, Rajamani J, Schaap-Nutt A, Huang KJ, Sommer MH, Chen YS, Chen YY, Arvin AM. Herpes simplex virus-1 induces expression of a novel MxA isoform that enhances viral replication. Immunol Cell Biol. 2011 Feb;89(2):173-82. doi: 10.1038/icb.2010.83. Epub 2010 Jul, 6. PMID:20603636 doi:10.1038/icb.2010.83
- ↑ Kochs G, Janzen C, Hohenberg H, Haller O. Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3153-8. PMID:11880649 doi:10.1073/pnas.052430399
- ↑ Andersson I, Bladh L, Mousavi-Jazi M, Magnusson KE, Lundkvist A, Haller O, Mirazimi A. Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus. J Virol. 2004 Apr;78(8):4323-9. PMID:15047845
- ↑ Turan K, Mibayashi M, Sugiyama K, Saito S, Numajiri A, Nagata K. Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res. 2004 Jan 29;32(2):643-52. Print 2004. PMID:14752052 doi:10.1093/nar/gkh192
- ↑ Reichelt M, Stertz S, Krijnse-Locker J, Haller O, Kochs G. Missorting of LaCrosse virus nucleocapsid protein by the interferon-induced MxA GTPase involves smooth ER membranes. Traffic. 2004 Oct;5(10):772-84. PMID:15355513 doi:10.1111/j.1600-0854.2004.00219.x
- ↑ Bridgen A, Dalrymple DA, Weber F, Elliott RM. Inhibition of Dugbe nairovirus replication by human MxA protein. Virus Res. 2004 Jan;99(1):47-50. PMID:14687945
- ↑ Lussier MP, Cayouette S, Lepage PK, Bernier CL, Francoeur N, St-Hilaire M, Pinard M, Boulay G. MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC. J Biol Chem. 2005 May 13;280(19):19393-400. Epub 2005 Mar 9. PMID:15757897 doi:10.1074/jbc.M500391200
- ↑ Kochs G, Reichelt M, Danino D, Hinshaw JE, Haller O. Assay and functional analysis of dynamin-like Mx proteins. Methods Enzymol. 2005;404:632-43. PMID:16413306 doi:10.1016/S0076-6879(05)04055-3
- ↑ Leroy M, Pire G, Baise E, Desmecht D. Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus. Neurobiol Dis. 2006 Mar;21(3):515-21. Epub 2005 Oct 3. PMID:16202617 doi:10.1016/j.nbd.2005.08.015
- ↑ Mundt E. Human MxA protein confers resistance to double-stranded RNA viruses of two virus families. J Gen Virol. 2007 Apr;88(Pt 4):1319-23. PMID:17374778 doi:10.1099/vir.0.82526-0
- ↑ Yu Z, Wang Z, Chen J, Li H, Lin Z, Zhang F, Zhou Y, Hou J. GTPase activity is not essential for the interferon-inducible MxA protein to inhibit the replication of hepatitis B virus. Arch Virol. 2008;153(9):1677-84. doi: 10.1007/s00705-008-0168-9. Epub 2008 Aug 1. PMID:18668195 doi:10.1007/s00705-008-0168-9
- ↑ Netherton CL, Simpson J, Haller O, Wileman TE, Takamatsu HH, Monaghan P, Taylor G. Inhibition of a large double-stranded DNA virus by MxA protein. J Virol. 2009 Mar;83(5):2310-20. doi: 10.1128/JVI.00781-08. Epub 2008 Dec 24. PMID:19109387 doi:10.1128/JVI.00781-08
- ↑ von der Malsburg A, Abutbul-Ionita I, Haller O, Kochs G, Danino D. Stalk domain of the dynamin-like MxA GTPase protein mediates membrane binding and liposome tubulation via the unstructured L4 loop. J Biol Chem. 2011 Oct 28;286(43):37858-65. doi: 10.1074/jbc.M111.249037. Epub, 2011 Sep 7. PMID:21900240 doi:10.1074/jbc.M111.249037
- ↑ Numajiri Haruki A, Naito T, Nishie T, Saito S, Nagata K. Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress. J Interferon Cytokine Res. 2011 Nov;31(11):847-56. doi: 10.1089/jir.2010.0132., Epub 2011 Oct 12. PMID:21992152 doi:10.1089/jir.2010.0132
- ↑ Gao S, von der Malsburg A, Paeschke S, Behlke J, Haller O, Kochs G, Daumke O. Structural basis of oligomerization in the stalk region of dynamin-like MxA. Nature. 2010 May 27;465(7297):502-6. Epub 2010 Apr 28. PMID:20428112 doi:10.1038/nature08972
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