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Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers
Georg Kochs1, Markus Haener, Ueli Aebi
1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany. kochs@ukl.uni-freiburg.de
Abstract:
Human MxA protein is a member of the interferon-induced Mx protein family and an important component of the innate host defense against RNA viruses. The Mx family belongs to a superfamily of large GTPases that also includes the dynamins and the interferon-regulated guanylate-binding proteins. A common feature of these large GTPases is their ability to form high molecular weight oligomers. Here we determined the capacity of MxA to self-assemble into homo-oligomers in vitro. We show that recombinant MxA protein assembles into long filamentous structures with a diameter of about 20 nm at physiological salt concentration as demonstrated by sedimentation assays and electron microscopy. In the presence of guanosine nucleotides the filaments rearranged into rings and more compact helical arrays. Our data indicate that binding and hydrolysis of GTP induce conformational changes in MxA that may be essential for viral target recognition and antiviral activity.
Insights
Human MxA protein, an interferon-induced antiviral factor, self-assembles into filaments and rings. GTP binding and hydrolysis drive conformational changes crucial for its antiviral activity against RNA viruses.
Area of Science:
- Molecular biology
- Virology
- Immunology
Background:
- Human MxA protein is key to innate immunity against RNA viruses.
- MxA belongs to the large GTPase superfamily, including dynamins and guanylate-binding proteins.
- Large GTPases share the characteristic of forming high molecular weight oligomers.
Purpose of the Study:
- To investigate the in vitro self-assembly capacity of human MxA protein.
- To understand the structural rearrangements of MxA in response to guanosine nucleotides.
Main Methods:
- Sedimentation assays
- Electron microscopy
- In vitro recombinant protein expression and assembly studies
Main Results:
- Recombinant MxA protein forms long filamentous structures (approx. 20 nm diameter) at physiological salt concentrations.
- In the presence of guanosine nucleotides, MxA filaments rearrange into rings and compact helical arrays.
- GTP binding and hydrolysis induce conformational changes in MxA.
Conclusions:
- Human MxA protein self-assembles into higher-order structures.
- GTP binding and hydrolysis are critical for MxA's conformational dynamics.
- These conformational changes are likely essential for MxA's viral target recognition and antiviral function.