Comparative modeling of human NSF reveals a possible binding mode of GABARAP and GATE-16.
Vesicular trafficking is an important homeostatic process in eukaryotic cells which critically relies on membrane fusion. One of the essential components of the universal membrane fusion machinery is NSF (N-ethylmaleimide-sensitive factor), a large hexameric ATPase involved in disassembly of SNARE (soluble NSF attachment protein receptor) complexes. To improve our understanding of this sophisticated molecular machine, we have modeled the structure of the NSF hexamer in two alternative assemblies. Our data suggest a mechanistic concept of the operating mode of NSF which helps to explain the functional impact of post-translational modifications and mutations reported previously. Furthermore, we propose a binding site for the ubiquitin-like proteins GABARAP and GATE-16, which is supported by experimental evidence, yielding a complex with favorable surface complementarity.
Thielmann
Yvonne
Y
Institut für Strukturbiologie und Biophysik 3 (Strukturbiochemie), Forschungszentrum Jülich, 52425 Jülich, Germany.
Weiergräber
Oliver H
OH
Ma
Peixiang
P
Schwarten
Melanie
M
Mohrlüder
Jeannine
J
Willbold
Dieter
D
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; D001665:Binding Sites; D006801:Humans; D006868:Hydrolysis; D008840:Microfilament Proteins / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008958:Models, Molecular; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; C116741:GABARAP protein, human; C498698:GABARAPL2 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D010455:Peptides; D025801:Ubiquitin; D000255:Adenosine Triphosphate; D052066:N-Ethylmaleimide-Sensitive Proteins