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The endoplasmic reticulum (ER) has often been described as the Grand Central Station within the living cell. This complex network of membrane sacks and tubules surrounding the nucleus is a major crossroads for synthesis, folding, modification, and transport of many important biological molecules. How is this intricate membrane structure formed and maintained? Researchers have recently discovered a family of proteins called atlastins that appear to be necessary for healthy ER structure. Now Byrnes and Sondermann (Cornell University) have solved two independent structures that shed new light on how pairs of atlastin molecules can induce opposing membrane surfaces to come together and fuse. Understanding the molecular basis for this fusion is an important step towards improved diagnosis and treatment of hereditary spastic paraplegia (HSP), a neurodegenerative disorder that occurs in childhood.
Byrnes, L. J. & Sondermann, H.; “Structural Basis for the Nucleotide-dependent Dimerization of the Large G Protein Atlastin-1/SPG3A”, Proceedings of the National Academy of Sciences 108, 2216-2221 (2011).
The arms of atlastin molecules in the extended configuration (form 2) bind to separate membrane surfaces. As GTP is converted to GDP within the molecules, the arms come together forcing the membranes to fuse into a three-way junction (lower left). These types of junctions are essential for the continuity of the endoplasmic reticulum.
In addition to crystallography, Byrnes and Sondermann used biological small-angle x-ray solution scattering (BioSAXS) data acquired at the Cornell High Energy Synchrotron Source (CHESS) to investigate the conformation of atlastin in solution in the presence of bound GTP. The low-resolution shape reconstructions were shown to be consistent with the extended atlastin structure (form 2).
More details on how this work impacts the field can be found in the commentary by Daumke and Praefcke that accompanied the article: Daumke, O. & Praefcke, G. J. K.; “Structural Insights into Membrane Fusion at the Endoplasmic Reticulum”, Proceedings of the National Academy of Sciences 108, 2175-2176 (2011).
Submitted by: Richard Gillilan, MacCHESS, Cornell University