Common core structure of amyloid fibrils by synchrotron X-ray diffraction 1 1Edited by F. E. Cohen

Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins?

“…These proteins are unrelated at the level of primary structure, consistent with the finding that many proteins with no connection to disease can form amyloid fibrils with a common core structure in vitro, suggesting that the amyloid fibril is an intrinsically stable structure (Dobson, 2001). Amyloid fibrils are not crystalline, so their structural similarity is based on lower-resolution approaches : X-ray fibril diffraction, electron and atomic force microscopy, and their ability to bind histopathological dyes like Congo Red and Thioflavin T (Sunde et al 1997). The structural convergence among various amyloid fibrils is also corroborated by the findings that antibodies Kayed et al 2003Lashuel et al 1998Sousa et al 2001Teng et al 2001Azimov et al 2001 Type II diabetes IAPP Anguiano et al 2002 ;Green et al 2003 ;Green, 2004 ;Kayed et al 2003 ;Porat et al 2003 ;Rhoades & Gafni, 2003Butler et al 2003de Koning et al 1994 ;Janson et al 1996 ;O'Brien et al 1994Janson et al 1999Anguiano, 2002 ;Porat et al 2003Anguiano et al 2002Harroun et al 2001 ;Hirakura et al 2000b ;Mirzabekov et al 1996 ;Porat et al 2003P53 Ishimaru et al 2003Ishimaru et al 2003Equine lysozyme Malisauskas et al 2003Malisauskas et al 2003Insulin Dzwolak et al 2005Dzwolak et al 2005 raised against the fibrillar form of the amyloidogenic protein amyloid-b (Ab ) recognize amyloid fibrils derived from other amyloid-forming proteins (O'Nuallain & Wetzel, 2002).…”

Annular Structures as Intermediates in Fibril Formation of Alzheimer Aβ17−42

“…The major components of these plaques are amyloid-β (Aβ) peptides consisting of a 40-42-residues cleaved by β-and γ-secretases from the transmembrane amyloid precursor protein (APP). Aβ fibrils, similar to fibrils associated with other neurodegenerative diseases such as Parkinson and Huntington diseases, have a high content of a cross-β pattern 5 , in which β-strands are arranged perpendicular to the fibrillar axis and form intermolecular parallel β-sheets with typical diameters of 10 nm and lengths up to several micrometers 6 . It has been suggested that nearly all native proteins and some synthetic peptides have the ability to form amyloids under appropriate conditions 7,8 , implying that general principles could govern amyloid fibril formation 9 .…”

Struktur von Amyloidfibrillen

“…Abb. 1 a; [23]). Die β-Faltblätter werden durch regelmäßige, lineare Stapel von Polypeptiden gebildet, die das zentrale strukturelle Charakteristikum von Amyloidfibrillen darstellen.…”

“…Die β-Faltblätter werden durch regelmäßige, lineare Stapel von Polypeptiden gebildet, die das zentrale strukturelle Charakteristikum von Amyloidfibrillen darstellen. Eine Amyloidfibrille kann aus einem oder mehreren nebeneinander liegenden β-Faltblättern dieses Typs bestehen [23].…”

“…Abb. 1 b; [23]). Die dominante meridionale Reflexion wird durch den Molekülabstand zwischen übereinander liegenden β-Strängen eines β-Faltblatts verursacht, der durch die Standardlänge der Wasserstoffbrü-ckenbindungen zwischen den β-Strängen auf etwa 4,7 Å fixiert ist.…”