Cover Picture: Molecular Origin of pH‐Dependent Fibril Formation of a Functional Amyloid (ChemBioChem 11/2014). Issue 11 (21st July 2014)

• Record Type: Journal Article
• Authors: McGlinchey, Ryan P.; Jiang, Zhiping; Lee, Jennifer C.
• Is Part Of: Chembiochem. Volume 15:Issue 11(2014)
• Page Start: 1529
• Page End: 1529
• Publication Date: 2014-07-21
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201490036
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>The cover picture shows</bold> 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 <ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">p. 1569 ff.</ext-link>, 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.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pght9226jw" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>