Monitoring the Interaction of α‐Synuclein with Calcium Ions through Exclusively Heteronuclear Nuclear Magnetic Resonance Experiments. (15th September 2020)

• Record Type: Journal Article
• Authors: Pontoriero, Letizia; Schiavina, Marco; Murrali, Maria Grazia; Pierattelli, Roberta; Felli, Isabella C.
• Is Part Of: Angewandte Chemie. Volume 132:Number 42(2020)
• Page Start: 18696
• Page End: 18704
• Publication Date: 2020-09-15
• Subjects: 13C detection -- calcium binding -- IDPs -- side chains -- water exchange; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202008079
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Many properties of intrinsically disordered proteins (IDPs), or protein regions (IDRs), are modulated by the nature of amino acid side chains as well as by local solvent exposure. We propose a set of exclusively heteronuclear NMR experiments to investigate these features in different experimental conditions that are relevant for physiological function. The proposed approach is generally applicable to many IDPs/IDRs whose assignment is available in the Biological Magnetic Resonance Bank (BMRB) to investigate how their properties are modulated by different, physiologically relevant conditions. The experiments, tested on α‐synuclein, are then used to investigate how α‐synuclein senses Ca 2+ concentration jumps associated with the transmission of nerve signals. Novel modules in the primary sequence of α‐synuclein optimized for calcium sensing in highly flexible, disordered protein segments are identified. Abstract : A set of exclusively heteronuclear NMR experiments is presented, which are tailored to zoom in on the side chains of intrinsically disordered proteins (IDPs). The interactions of α‐synuclein with Ca 2+ ions were monitored, and the local solvent exposure in the presence and absence of Ca 2+ studied with a 13 C direct detection approach. Novel modules optimized for calcium sensing were identified in the primary sequence of α‐synuclein.