2MPZ
Atomic model of the Abeta D23N "Iowa" mutant using solid-state NMR, EM and Rosetta modeling
Summary for 2MPZ
| Entry DOI | 10.2210/pdb2mpz/pdb |
| NMR Information | BMRB: 25004 |
| Descriptor | Amyloid beta A4 protein (1 entity in total) |
| Functional Keywords | amyloid, polymorhpism, sparse data, hybrid methods, protein fibril |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P05067 |
| Total number of polymer chains | 27 |
| Total formula weight | 71553.89 |
| Authors | Sgourakis, N.G.,Qiang, W. (deposition date: 2014-06-10, release date: 2015-04-22, Last modification date: 2024-05-01) |
| Primary citation | Sgourakis, N.G.,Yau, W.M.,Qiang, W. Modeling an in-register, parallel "iowa" a beta fibril structure using solid-state NMR data from labeled samples with rosetta. Structure, 23:216-227, 2015 Cited by PubMed Abstract: Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For β-amyloid (Aβ) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of Aβ using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper" core interactions are determined using a number of solid-state NMR techniques on sparsely (13)C-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa" mutant (D23N) at high resolution (1.2Å backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features. PubMed: 25543257DOI: 10.1016/j.str.2014.10.022 PDB entries with the same primary citation |
| Experimental method | SOLID-STATE NMR |
Structure validation
Download full validation report
