TY - JOUR
T1 - Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein
AU - Wongkongkathep, Piriya
AU - Han, Jong Yoon
AU - Choi, Tae Su
AU - Yin, Sheng
AU - Kim, Hugh I.
AU - Loo, Joseph A.
N1 - Funding Information:
This study received support from the US National Institutes of Health (R01GM103479, S10RR028893, S10OD018504 to J.A.L.); the US Department of Energy (DE-FC02-02ER63421 to J.A.L.); the Development and Promotion of Science and Technology Talents Project (DPST) and Royal Thai Government (to P.W.); the Rachadapisek Sompot Fund, Chulalongkorn University (to P.W.); the National Research Foundation of Korea (NRF) (NRF-2016R1A2B4013089 and 20100020209 to H.I.K.); Korea University Future Research Grant (to H.I.K.); and the Ministry of Science, ICT and Future Planning (CAP-15-10-KRICT to H.I.K.).
Publisher Copyright:
© 2018, American Society for Mass Spectrometry.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].
AB - Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].
KW - Electron capture dissociation
KW - Electrospray ionization
KW - Metal binding
KW - Native mass spectrometry
KW - Protein-ligand complex
KW - Top-down mass spectrometry
KW - α-Synuclein
UR - http://www.scopus.com/inward/record.url?scp=85051446010&partnerID=8YFLogxK
U2 - 10.1007/s13361-018-2002-2
DO - 10.1007/s13361-018-2002-2
M3 - Article
C2 - 29951842
AN - SCOPUS:85051446010
SN - 1044-0305
VL - 29
SP - 1870
EP - 1880
JO - Journal of the American Society for Mass Spectrometry
JF - Journal of the American Society for Mass Spectrometry
IS - 9
ER -