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dc.contributor.authorBaumann, Anneen_US
dc.contributor.authorGjerde, Anja Underhaugen_US
dc.contributor.authorYing, Mingen_US
dc.contributor.authorSvanborg, Catharinaen_US
dc.contributor.authorHolmsen, Holm A.en_US
dc.contributor.authorGlomm, Wilhelmen_US
dc.contributor.authorMartinez, Auroraen_US
dc.contributor.authorHalskau, Øyvinden_US
dc.description.abstractRecently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75–100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutralpH—as observed by liposome content leakage and circular dichroism experiments—and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET.en_US
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.subjectMembrane bindingeng
dc.subjectpore formationeng
dc.titleHAMLET forms annular oligomers when deposited with phoshpolipid monolayersen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2012 Elsevier Ltd.
dc.source.journalJournal of Molecular Biology
dc.subject.nsiVDP::Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical molecular biology: 711eng
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi : 711nob

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