2M5N

Atomic-resolution structure of a cross-beta protofilament

Summary for 2M5N

• Entry DOI: 10.2210/pdb2m5n/pdb
• Related: 2M5K 2M5M 3ZPK
• NMR Information: BMRB: 19062
• Descriptor: Transthyretin (1 entity in total)
• Functional Keywords: amyloid fibril, cross-beta structure, protein fibril
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 16
• Total formula weight: 19173.86

Authors

Fitzpatrick, A.W.P.,Debelouchina, G.T.,Bayro, M.J.,Clare, D.K.,Caporini, M.A.,Bajaj, V.S.,Jaroniec, C.P.,Wang, L.,Ladizhansky, V.,Muller, S.,MacPhee, C.E.,Waudby, C.A.,Mott, H.R.,de Simone, A.,Knowles, T.P.J.,Saibil, H.R.,Vendruscolo, M.,Orlova, E.V.,Griffin, R.G.,Dobson, C.M. (deposition date: 2013-02-27, release date: 2013-07-17, Last modification date: 2024-05-15)

Primary citation

Fitzpatrick, A.W.,Debelouchina, G.T.,Bayro, M.J.,Clare, D.K.,Caporini, M.A.,Bajaj, V.S.,Jaroniec, C.P.,Wang, L.,Ladizhansky, V.,Muller, S.A.,MacPhee, C.E.,Waudby, C.A.,Mott, H.R.,De Simone, A.,Knowles, T.P.,Saibil, H.R.,Vendruscolo, M.,Orlova, E.V.,Griffin, R.G.,Dobson, C.M.
Atomic structure and hierarchical assembly of a cross-{beta} amyloid fibril.
Proc.Natl.Acad.Sci.USA, 110:5468-5473, 2013

PubMed Abstract: The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale--including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy--we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.

PubMed: 23513222
DOI: 10.1073/pnas.1219476110

Experimental method

SOLID-STATE NMR