Three-dimensional structure of AAA ATPase Vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding.
Vps4 is a AAA ATPase that mediates endosomal membrane protein sorting. It is also a host factor hijacked by a diverse set of clinically important viruses, including HIV and Ebola, to facilitate viral budding. Here we present the three-dimensional structure of the hydrolysis-defective Vps4p(E233Q) mutant. Single-particle analysis, multiangle laser light scattering, and the docking of independently determined atomic models of Vps4 monomers reveal a complex with C6 point symmetry, distinguishing between a range of previously suggested oligomeric states (8-14 subunits). The 3D reconstruction also reveals a tail-to-tail subunit organization between the two rings of the complex and identifies the location of domains critical to complex assembly and interaction with partner proteins. Our refined Vps4 structure is better supported by independent lines of evidence than those previously proposed, and provides insights into the mechanism of endosomal membrane protein sorting and viral envelope budding.
Landsberg
Michael John
MJ
Institute for Molecular Bioscience, The University of Queensland, St. Lucia QLD 4072, Australia.
Vajjhala
Parimala Rao
PR
Rothnagel
Rosalba
R
Munn
Alan Leslie
AL
Hankamer
Ben
B
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D002850:Chromatography, Gel; D019281:Dimerization; D011992:Endosomes / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D021381:Protein Transport; D013329:Structure-Activity Relationship; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D018406:Virus Physiological Phenomena
D005656:Fungal Proteins; D033921:Vesicular Transport Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases