A novel amyloid designable scaffold and potential inhibitor inspired by GAIIG of amyloid beta and the HIV-1 V3 loop

作者：Kokotidou Chrysoula; Jonnalagadda Sai Vamshi R; Orr Asuka A; Seoane Blanco Mateo; Apostolidou Chrysanthi Pinelopi; van Raaij Mark J; Kotzabasaki Marianna; Chatzoudis Apostolos; Jakubowski Joseph M; Mossou Estelle; Forsyth V Trevor; Mitchell Edward P; Bowler Matthew W; Llamas Saiz Antonio L^*; Tamamis Phanourios^*; Mitraki Anna^*

来源：FEBS LETTERS, 2018, 592(11): 1777-1788.

DOI：10.1002/1873-3468.13096

• amyloid
• beta-breaker
• peptide self-assembly

The GAIIG sequence, common to the amyloid beta peptide (residues 29-33) and to the HIV-1 gp120 (residues 24-28 in a typical V3 loop), self-assembles into amyloid fibrils, as suggested by theory and the experiments presented here. The longer YATGAIIGNII sequence from the V3 loop also self-assembles into amyloid fibrils, of which the first three and the last two residues are outside the amyloid GAIIG core. We postulate that this sequence, with suitably selected modifications at the flexible positions, can serve as a designable scaffold for novel amyloid-based materials. Moreover, we report the single crystal X-ray structure of the beta-breaker peptide GAIPIG at 1.05 angstrom resolution. The structural information provided in this study could serve as the basis for structure-based design of potential inhibitors of amyloid formation.

• 出版日期2018-6