Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers.
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.
Kochs
Georg
G
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany. kochs@ukl.uni-freiburg.de
Haener
Markus
M
Aebi
Ueli
U
Haller
Otto
O
D017607:Aluminum Compounds / Q000494:pharmacology; D019281:Dimerization; D034281:Dynamins; D004926:Escherichia coli / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism*; D019204:GTP-Binding Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D064547:Myxovirus Resistance Proteins; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012492:Salts / Q000494:pharmacology
D017607:Aluminum Compounds; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012492:Salts; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D034281:Dynamins; D005459:Fluorides; C032311:aluminum fluoride