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Small-angle X-ray scattering of BAMLET at pH 12 : a complex of α-lactalbumin and oleic acid

Rath, Emma M; Duff, Anthony P; Håkansson, Anders P LU ; Knott, Robert B and Church, W Bret (2014) In Proteins 82(7). p.8-1400
Abstract

BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration. Increases in oleic acid concentration correlate with increasing radius of gyration without an increase in maximum particle dimension, indicating decreasing protein density. The... (More)

BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration. Increases in oleic acid concentration correlate with increasing radius of gyration without an increase in maximum particle dimension, indicating decreasing protein density. The models for the highest oleic acid content BAMLET indicate an unusual coiled elongated structure that contrasts with apo-α-lactalbumin at pH 12, which is an elongated globular molecule, suggesting that oleic acid inhibits the folding or collapse of the protein component of BAMLET to the globular form. Circular dichroism of BAMLET and apo-α-lactalbumin was performed and the results suggest that α-lactalbumin and BAMLET unfold in a continuum of increasing degree of unfolded states. Taken together, these results support a model in which BAMLET retains oleic acid by non-specific association in the core of partially unfolded protein, and represent a new type of lipoprotein structure.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Cattle, Circular Dichroism, Hydrogen-Ion Concentration, Lactalbumin, Models, Molecular, Oleic Acid, Scattering, Small Angle, X-Ray Diffraction
in
Proteins
volume
82
issue
7
pages
9 pages
publisher
John Wiley & Sons
external identifiers
  • Scopus:84902205898
ISSN
0887-3585
DOI
10.1002/prot.24508
language
English
LU publication?
yes
id
aaa1da56-5738-4d32-9d2f-929731411a78
date added to LUP
2016-05-21 10:48:02
date last changed
2016-10-30 04:47:45
@misc{aaa1da56-5738-4d32-9d2f-929731411a78,
  abstract     = {<p>BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration. Increases in oleic acid concentration correlate with increasing radius of gyration without an increase in maximum particle dimension, indicating decreasing protein density. The models for the highest oleic acid content BAMLET indicate an unusual coiled elongated structure that contrasts with apo-α-lactalbumin at pH 12, which is an elongated globular molecule, suggesting that oleic acid inhibits the folding or collapse of the protein component of BAMLET to the globular form. Circular dichroism of BAMLET and apo-α-lactalbumin was performed and the results suggest that α-lactalbumin and BAMLET unfold in a continuum of increasing degree of unfolded states. Taken together, these results support a model in which BAMLET retains oleic acid by non-specific association in the core of partially unfolded protein, and represent a new type of lipoprotein structure.</p>},
  author       = {Rath, Emma M and Duff, Anthony P and Håkansson, Anders P and Knott, Robert B and Church, W Bret},
  issn         = {0887-3585},
  keyword      = {Animals,Cattle,Circular Dichroism,Hydrogen-Ion Concentration,Lactalbumin,Models, Molecular,Oleic Acid,Scattering, Small Angle,X-Ray Diffraction},
  language     = {eng},
  number       = {7},
  pages        = {8--1400},
  publisher    = {ARRAY(0x99816f8)},
  series       = {Proteins},
  title        = {Small-angle X-ray scattering of BAMLET at pH 12 : a complex of α-lactalbumin and oleic acid},
  url          = {http://dx.doi.org/10.1002/prot.24508},
  volume       = {82},
  year         = {2014},
}