Atlastin, a member of the dynamin superfamily, is known to catalyse homotypic membrane fusion in the smooth endoplasmic reticulum (ER). Recent studies of atlastin have elucidated key features about its structure and function; however, several mechanistic details, including the catalytic mechanism and GTP hydrolysis-driven conformational changes, are yet to be determined. Here, we present the crystal structures of atlastin-1 bound to GDP center dot AlF4- and GppNHp, uncovering an intramolecular arginine finger that stimulates GTP hydrolysis when correctly oriented through rearrangements within the G domain. Utilizing Forster Resonance Energy Transfer, we describe nucleotide binding and hydrolysis-driven conformational changes in atlastin and their sequence. Furthermore, we discovered a nucleotide exchange mechanism that is intrinsic to atlastin's N-terminal domains. Our results indicate that the cytoplasmic domain of atlastin acts as a tether and homotypic interactions are timed by GTP binding and hydrolysis. Perturbation of these mechanisms may be implicated in a group of atlastin-associated hereditary neurodegenerative diseases.
机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Liu, Tina Y.
Bian, Xin
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Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Bian, Xin
Sun, Sha
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Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Sun, Sha
Hu, Xiaoyu
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Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Hu, Xiaoyu
Klemm, Robin W.
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机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Klemm, Robin W.
Prinz, William A.
论文数: 0引用数: 0
h-index: 0
机构:
NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Prinz, William A.
Rapoport, Tom A.
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机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Rapoport, Tom A.
Hu, Junjie
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机构:
Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Park, Seong H.
Zhu, Peng-Peng
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NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Zhu, Peng-Peng
Parker, Rell L.
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NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Parker, Rell L.
Blackstone, Craig
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机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Liu, Tina Y.
Bian, Xin
论文数: 0引用数: 0
h-index: 0
机构:
Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Bian, Xin
Sun, Sha
论文数: 0引用数: 0
h-index: 0
机构:
Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Sun, Sha
Hu, Xiaoyu
论文数: 0引用数: 0
h-index: 0
机构:
Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Hu, Xiaoyu
Klemm, Robin W.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Klemm, Robin W.
Prinz, William A.
论文数: 0引用数: 0
h-index: 0
机构:
NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Prinz, William A.
Rapoport, Tom A.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USANankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Rapoport, Tom A.
Hu, Junjie
论文数: 0引用数: 0
h-index: 0
机构:
Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R ChinaNankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Park, Seong H.
Zhu, Peng-Peng
论文数: 0引用数: 0
h-index: 0
机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Zhu, Peng-Peng
Parker, Rell L.
论文数: 0引用数: 0
h-index: 0
机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA
Parker, Rell L.
Blackstone, Craig
论文数: 0引用数: 0
h-index: 0
机构:
NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USANINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA