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A novel amyloid designable scaffold and potential inhibitor inspired by GAIIG of amyloid beta and the HIV ‐1 V3 loop
Author(s) -
Kokotidou Chrysoula,
Jonnalagadda Sai Vamshi R.,
Orr Asuka A.,
SeoaneBlanco Mateo,
Apostolidou Chrysanthi Pinelopi,
Raaij Mark J.,
Kotzabasaki Marianna,
Chatzoudis Apostolos,
Jakubowski Joseph M.,
Mossou Estelle,
Forsyth V. Trevor,
Mitchell Edward P.,
Bowler Matthew W.,
LlamasSaiz Antonio L.,
Tamamis Phanourios,
Mitraki Anna
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13096
Subject(s) - amyloid (mycology) , beta (programming language) , human immunodeficiency virus (hiv) , chemistry , scaffold , loop (graph theory) , amyloid beta , biophysics , amyloid precursor protein , biochemistry , microbiology and biotechnology , virology , biology , computer science , peptide , alzheimer's disease , disease , medicine , inorganic chemistry , pathology , database , programming language , mathematics , combinatorics
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 Å resolution. The structural information provided in this study could serve as the basis for structure‐based design of potential inhibitors of amyloid formation.