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Structure of apolipoprotein A-I's N-terminus on nascent high density lipoprotein.

Lagerstedt, Jens LU ; Cavigiolio, Giorgio; Budamagunta, Madhu S; Pagani, Ioanna; Voss, John C and Oda, Michael N (2011) In Journal of Biological Chemistry 286(4). p.2966-2975
Abstract
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and a critical element of cholesterol metabolism. To better elucidate the role of apoA-I structure-function in cholesterol metabolism, the conformation of apoA-I's N-terminus (residues 6-98) on nascent HDL was examined by electron paramagnetic resonance (EPR) spectroscopic analysis. A series of 93 apoA-I variants bearing single nitroxide spin label at positions 6-98 was reconstituted onto 9.6 nm HDL particles (rHDL). These particles were subjected to EPR spectral analysis, measuring regional flexibility and side chain solvent accessibility. Secondary structure was elucidated from side-chain mobility and molecular accessibility, wherein two major... (More)
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and a critical element of cholesterol metabolism. To better elucidate the role of apoA-I structure-function in cholesterol metabolism, the conformation of apoA-I's N-terminus (residues 6-98) on nascent HDL was examined by electron paramagnetic resonance (EPR) spectroscopic analysis. A series of 93 apoA-I variants bearing single nitroxide spin label at positions 6-98 was reconstituted onto 9.6 nm HDL particles (rHDL). These particles were subjected to EPR spectral analysis, measuring regional flexibility and side chain solvent accessibility. Secondary structure was elucidated from side-chain mobility and molecular accessibility, wherein two major α-helical domains were localized to residues 6-34 and 50-98. We identified an unstructured segment (residues 35-39) and a β-strand (residues 40-49) between the two helices. Residues 14, 19, 34, 37, 41 and 58 were examined by EPR on 7.8, 8.4, and 9.6 nm rHDL to assess the effect of particle size on N-terminal structure. Residues 14, 19 and 58 showed no significant rHDL size-dependent spectral or accessibility differences, whereas residues 34, 37, and 41, displayed moderate spectral changes along with substantial rHDL size-dependent differences in molecular accessibility. We have elucidated the secondary structure of the N-terminal domain of apoA-I on 9.6 nm rHDL (residues 6-98) and identified residues in this region that are affected by particle size. We conclude that the inter-helical segment (residues 35-49) plays a role in apoA-I's adaptation to HDL particle size. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
286
issue
4
pages
2966 - 2975
publisher
ASBMB
external identifiers
  • wos:000286464300060
  • pmid:21047795
  • scopus:78951473336
ISSN
1083-351X
DOI
10.1074/jbc.M110.163097
language
English
LU publication?
yes
id
ef8dc721-5f44-4ada-87e0-2e31db3b4fdd (old id 1732347)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21047795?dopt=Abstract
date added to LUP
2010-12-01 10:12:26
date last changed
2017-10-08 03:03:08
@article{ef8dc721-5f44-4ada-87e0-2e31db3b4fdd,
  abstract     = {Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and a critical element of cholesterol metabolism. To better elucidate the role of apoA-I structure-function in cholesterol metabolism, the conformation of apoA-I's N-terminus (residues 6-98) on nascent HDL was examined by electron paramagnetic resonance (EPR) spectroscopic analysis. A series of 93 apoA-I variants bearing single nitroxide spin label at positions 6-98 was reconstituted onto 9.6 nm HDL particles (rHDL). These particles were subjected to EPR spectral analysis, measuring regional flexibility and side chain solvent accessibility. Secondary structure was elucidated from side-chain mobility and molecular accessibility, wherein two major α-helical domains were localized to residues 6-34 and 50-98. We identified an unstructured segment (residues 35-39) and a β-strand (residues 40-49) between the two helices. Residues 14, 19, 34, 37, 41 and 58 were examined by EPR on 7.8, 8.4, and 9.6 nm rHDL to assess the effect of particle size on N-terminal structure. Residues 14, 19 and 58 showed no significant rHDL size-dependent spectral or accessibility differences, whereas residues 34, 37, and 41, displayed moderate spectral changes along with substantial rHDL size-dependent differences in molecular accessibility. We have elucidated the secondary structure of the N-terminal domain of apoA-I on 9.6 nm rHDL (residues 6-98) and identified residues in this region that are affected by particle size. We conclude that the inter-helical segment (residues 35-49) plays a role in apoA-I's adaptation to HDL particle size.},
  author       = {Lagerstedt, Jens and Cavigiolio, Giorgio and Budamagunta, Madhu S and Pagani, Ioanna and Voss, John C and Oda, Michael N},
  issn         = {1083-351X},
  language     = {eng},
  number       = {4},
  pages        = {2966--2975},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Structure of apolipoprotein A-I's N-terminus on nascent high density lipoprotein.},
  url          = {http://dx.doi.org/10.1074/jbc.M110.163097},
  volume       = {286},
  year         = {2011},
}