4ZNN

MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56

4ZNN の概要

• エントリーDOI: 10.2210/pdb4znn/pdb
• 関連するPDBエントリー: 4RIL
• EMDBエントリー: 3001
• 分子名称: Alpha-synuclein (2 entities in total)
• 機能のキーワード: amyloid, alpha-synuclein, parkinson's disease, toxic core, nacore, lipid binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 940.07

構造登録者

Rodriguez, J.A.,Ivanova, M.,Sawaya, M.R.,Cascio, D.,Reyes, F.,Shi, D.,Johnson, L.,Guenther, E.,Sangwan, S.,Hattne, J.,Nannenga, B.,Brewster, A.S.,Messerschmidt, M.,Boutet, S.,Sauter, N.K.,Gonen, T.,Eisenberg, D.S. (登録日: 2015-05-05, 公開日: 2015-09-09, 最終更新日: 2024-03-06)

主引用文献

Rodriguez, J.A.,Ivanova, M.I.,Sawaya, M.R.,Cascio, D.,Reyes, F.E.,Shi, D.,Sangwan, S.,Guenther, E.L.,Johnson, L.M.,Zhang, M.,Jiang, L.,Arbing, M.A.,Nannenga, B.L.,Hattne, J.,Whitelegge, J.,Brewster, A.S.,Messerschmidt, M.,Boutet, S.,Sauter, N.K.,Gonen, T.,Eisenberg, D.S.
Structure of the toxic core of alpha-synuclein from invisible crystals.
Nature, 525:486-490, 2015

PubMed Abstract: The protein α-synuclein is the main component of Lewy bodies, the neuron-associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human α-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 Å resolution structure demonstrates that this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face β-sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length α-synuclein. The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length α-synuclein fibril, presenting opportunities for the design of inhibitors of α-synuclein fibrils.

PubMed: 26352473
DOI: 10.1038/nature15368

実験手法

ELECTRON CRYSTALLOGRAPHY (1.41 Å)