The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures

FEBS Letters

Flohr, Felix¹  Haller, Otto¹  Kochs, Georg¹  Schneider-Schaulies, Sibylle² 

[1] Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany;Institut für Virologie und Immunologie, Universität Würzburg, D-97078 Würzburg, Germany

关键词: MxA GTPase;    Dynamin superfamily;    Antiviral effect;    GED;    GTPase effector domain;    mAb;    monoclonal antibody;    THOV;    Thogoto virus;   

DOI  :  10.1016/S0014-5793(99)01598-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To define domains of the human MxA GTPase involved in GTP hydrolysis and antiviral activity, we used two monoclonal antibodies (mAb) directed against different regions of the molecule. mAb 2C12 recognizes an epitope in the central interactive region of MxA, whereas mAb M143 is directed against the N-terminal G domain. mAb 2C12 greatly stimulated MxA GTPase activity, suggesting that antibody-mediated crosslinking enhances GTP hydrolysis. In contrast, monovalent Fab fragments of 2C12 abolished GTPase activity, most likely by blocking intramolecular interactions required for GTPase activation. Interestingly, intact IgG molecules and Fab fragments of 2C12 both prevented association of MxA with viral nucleocapsids and neutralized MxA antiviral activity in vivo. mAb M143 had no effect on MxA function, indicating that this antibody binds outside functional regions. These data demonstrate that the central region recognized by 2C12 is critical for regulation of GTPase activity and viral target recognition.

【 授权许可】

Unknown