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Molecular characterization of alpha-lactalbumin folding variants that induce apoptosis in tumor cells

Svensson, Malin LU ; Sabharwal, H; Håkansson, Anders P LU ; Mossberg, A K LU ; Lipniunas, P; Leffler, H LU ; Svanborg, C LU and Linse, S LU (1999) In Journal of Biological Chemistry 274(10). p.6388-96
Abstract

This study characterized a protein complex in human milk that induces apoptosis in tumor cells but spares healthy cells. The active fraction was purified from casein by anion exchange chromatography. Unlike other casein components the active fraction was retained by the ion exchanger and eluted after a high salt gradient. The active fraction showed N-terminal amino acid sequence identity with human milk alpha-lactalbumin and mass spectrometry ruled out post-translational modifications. Size exclusion chromatography resolved monomers and oligomers of alpha-lactalbumin that were characterized using UV absorbance, fluorescence, and circular dichroism spectroscopy. The high molecular weight oligomers were kinetically stable against... (More)

This study characterized a protein complex in human milk that induces apoptosis in tumor cells but spares healthy cells. The active fraction was purified from casein by anion exchange chromatography. Unlike other casein components the active fraction was retained by the ion exchanger and eluted after a high salt gradient. The active fraction showed N-terminal amino acid sequence identity with human milk alpha-lactalbumin and mass spectrometry ruled out post-translational modifications. Size exclusion chromatography resolved monomers and oligomers of alpha-lactalbumin that were characterized using UV absorbance, fluorescence, and circular dichroism spectroscopy. The high molecular weight oligomers were kinetically stable against dissociation into monomers and were found to have an essentially retained secondary structure but a less well organized tertiary structure. Comparison with native monomeric and molten globule alpha-lactalbumin showed that the active fraction contains oligomers of alpha-lactalbumin that have undergone a conformational switch toward a molten globule-like state. Oligomerization appears to conserve alpha-lactalbumin in a state with molten globule-like properties at physiological conditions. The results suggest differences in biological properties between folding variants of alpha-lactalbumin.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amino Acid Sequence, Apoptosis, Dimerization, Female, Humans, Lactalbumin, Milk, Human, Molecular Sequence Data, Neoplasms, Protein Folding, Structure-Activity Relationship
in
Journal of Biological Chemistry
volume
274
issue
10
pages
9 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • Scopus:0033525523
ISSN
0021-9258
DOI
10.1074/jbc.274.10.6388
language
English
LU publication?
yes
id
8d1219fd-cf71-42bd-9552-5e00aecd7a54
date added to LUP
2016-05-21 11:28:52
date last changed
2016-06-09 14:34:50
@misc{8d1219fd-cf71-42bd-9552-5e00aecd7a54,
  abstract     = {<p>This study characterized a protein complex in human milk that induces apoptosis in tumor cells but spares healthy cells. The active fraction was purified from casein by anion exchange chromatography. Unlike other casein components the active fraction was retained by the ion exchanger and eluted after a high salt gradient. The active fraction showed N-terminal amino acid sequence identity with human milk alpha-lactalbumin and mass spectrometry ruled out post-translational modifications. Size exclusion chromatography resolved monomers and oligomers of alpha-lactalbumin that were characterized using UV absorbance, fluorescence, and circular dichroism spectroscopy. The high molecular weight oligomers were kinetically stable against dissociation into monomers and were found to have an essentially retained secondary structure but a less well organized tertiary structure. Comparison with native monomeric and molten globule alpha-lactalbumin showed that the active fraction contains oligomers of alpha-lactalbumin that have undergone a conformational switch toward a molten globule-like state. Oligomerization appears to conserve alpha-lactalbumin in a state with molten globule-like properties at physiological conditions. The results suggest differences in biological properties between folding variants of alpha-lactalbumin.</p>},
  author       = {Svensson, Malin and Sabharwal, H and Håkansson, Anders P and Mossberg, A K and Lipniunas, P and Leffler, H and Svanborg, C and Linse, S},
  issn         = {0021-9258},
  keyword      = {Amino Acid Sequence,Apoptosis,Dimerization,Female,Humans,Lactalbumin,Milk, Human,Molecular Sequence Data,Neoplasms,Protein Folding,Structure-Activity Relationship},
  language     = {eng},
  month        = {03},
  number       = {10},
  pages        = {6388--96},
  publisher    = {ARRAY(0xab0f378)},
  series       = {Journal of Biological Chemistry},
  title        = {Molecular characterization of alpha-lactalbumin folding variants that induce apoptosis in tumor cells},
  url          = {http://dx.doi.org/10.1074/jbc.274.10.6388},
  volume       = {274},
  year         = {1999},
}