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Cover Picture: Molecular Origin of pH‐Dependent Fibril Formation of a Functional Amyloid (ChemBioChem 11/2014)
Author(s) -
McGlinchey Ryan P.,
Jiang Zhiping,
Lee Jennifer C.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201490036
Subject(s) - fibril , chemistry , protonation , deprotonation , residue (chemistry) , polymerization , amyloid (mycology) , biophysics , static electricity , dissolution , amyloid fibril , crystallography , stereochemistry , amyloid β , biochemistry , organic chemistry , polymer , ion , inorganic chemistry , medicine , disease , pathology , biology , engineering , electrical engineering
The cover picture shows the reversible, pH‐dependent fibril formation of the functional amyloid Pmel17 repeat domain. This unique polymerization process contrasts with that of disease‐related amyloids, which resist the harshest of treatments, and thereby provides an effective way of controlling amyloid assembly. On p. 1569 ff. , J. C. Lee et al. show that fibrils only form under mildly acidic pH (5±0.5) and completely dissolve at neutral pH. By using mutational analysis, it was determined that protonation of a single glutamic acid residue (out of the 16 carboxylic acids) is responsible for fibril formation and stability. Remarkably, removal of this single negative charge shifted the pH dependence by a full pH unit. Deprotonation of this residue results in intrasheet electrostatic repulsion and causes fibril dissolution at pH≥6.