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HAMLET Forms Annular Oligomers When Deposited with Phospholipid Monolayers

På svenska

Author

  • Anne Baumann
  • Anja Underhaug Gjerde
  • Ming Ying
  • Catharina Svanborg
  • Holm Holmsen
  • Wilhelm R. Glomm
  • Aurora Martinez
  • Oyvind Halskau

Summary, in English

Recently, the anticancer activity of human a-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 alpha-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 neutral pH 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. (C) 2012 Elsevier Ltd. All rights reserved.

Publishing year

2012

Language

English

Pages

90-102

Publication/Series

Journal of Molecular Biology

Volume

418

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Immunology in the medical area
  • Microbiology in the medical area

Keywords

  • alpha-lactalbumin
  • membrane binding
  • pore formation
  • leakage
  • AFM

Status

Published

ISBN/ISSN/Other

  • ISSN: 1089-8638