Journal article

A structural core within apolipoprotein C-II amyloid fibrils identified using hydrogen exchange and proteolysis

Leanne M Wilson, Yee-Foong Mok, Katrina J Binger, Michael DW Griffin, Haydyn DT Mertens, Feng Lin, John D Wade, Paul R Gooley, Geoffrey J Howlett

JOURNAL OF MOLECULAR BIOLOGY | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2007

Abstract

Plasma apolipoproteins show alpha-helical structure in the lipid-bound state and limited conformational stability in the absence of lipid. This structural instability of lipid-free apolipoproteins may account for the high propensity of apolipoproteins to aggregate and accumulate in disease-related amyloid deposits. Here, we explore the properties of amyloid fibrils formed by apolipoproteins using human apolipoprotein (apo) C-II as a model system. Hydrogen-deuterium exchange and NMR spectroscopy of apoC-II fibrils revealed core regions between residues 19-37 and 57-74 with reduced amide proton exchange rates compared to monomeric apoC-II. The C-terminal core region was also identified by part..

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