TAILIEUCHUNG - Báo cáo Y học: Solution structure of the Alzheimer amyloid b-peptide (1–42) in an apolar microenvironment Similarity with a virus fusion domain

The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid b-peptides (Ab),which derive from the proteolitic cleavage of conformational transition from a soluble form to aggrega-ted,fibrillary b-sheet structures,which seem to be neuro-toxic. Alternatively,it has been suggested that ana-helical form can be involved in a process of membrane poration, which would then trigger cellular death. | Eur. J. Biochem. 269 _ 4 _2 _M 4 S 2002 FEBS 2002 doi Solution structure of the Alzheimer amyloid b-peptide 1-42 in an apolar microenvironment Similarity with a virus fusion domain Orlando Crescenzi1 Simona Tomaselli1 Remo Guerrini2 Severo Salvador 2 Anna M. D Ursi3 Piero Andrea Temussi1 and Delia Picone1 1 Dipartimento di Chimica Universita degli Studi di Napoli Federico II Italy 2Dipartimento di Scienze Farmaceutiche Universita di Ferrara Italy 3Dipartimento di Scienze Farmaceutiche Universita di Salerno Italy The major components of neuritic plaques found in Alzheimer disease AD are peptides known as amyloid b-peptides Ab which derive from the proteoiitic c eavaae of the amyloid precursor proteins. In vitro Ab may undergo a conformational transition from a soluble form to aggregated llbrí Hui v b-sheet structures which eem to be eeurotoxic. Alternatively ít has been u iggesedl that an a-helical form can be iniolied in a process of membrane poration which would then trigger cellular death. Conformational studies on these peptides in aqueous solution are complicated by their tendency to aggregate and only recently NMR structures of Ab- 1-40 and Ab- 1-42 have been determined in aqueous trifluoroethanol or in SDS micelles. All these studies hint to the presence of two helical regions connected through a flexible kink uut it povedd dil iiuult to hutemblte ihe 1 12111 and position of the helical stretches with accuracy and most of all to aseertam whihhel lite kikk tetren ass a preferred conformation. In the search for a medium which could allow a more accurate structure determination we performed an exhaustive solvent scan that showed a high propensity of Ab- 1-42 to adopt helical conformations in aqueous solutions of fluorinated alcohols. The 3D NMR structure of Ab- 1-42 shows two helical regions encompassing residues 8-25 and 28-38 r Oi hsseed by a tegulpr type I b-turn. The surprising similarity of this structure as well as the .

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