Mouse ApoM Displays an Unprecedented Seven-Stranded Lipocalin Fold: Folding Decoy or Alternative Native Fold?
(2010) In Journal of Molecular Biology 404(3). p.363-371- Abstract
- Mouse apolipoprotein M (m-apoM) displays a 79% sequence identity to human apolipoprotein M (h-apoM). Both proteins are apolipoproteins associated with high-density lipoproteins, with similar anticipated biological functions. The structure of h-apoM has recently been determined by X-ray crystallography, which revealed that h-apoM displays, as expected, a lipocalin-like fold characterized by an eight-stranded 13 barrel that encloses an internal fatty-acid-binding site. Surprisingly, this is not true for m-apoM. After refolding from inclusion bodies, the crystal structure of m-apoM (reported here at 2.5 angstrom resolution) displays a novel yet unprecedented seven-stranded beta-barrel structure. The fold difference is not caused by a mere... (More)
- Mouse apolipoprotein M (m-apoM) displays a 79% sequence identity to human apolipoprotein M (h-apoM). Both proteins are apolipoproteins associated with high-density lipoproteins, with similar anticipated biological functions. The structure of h-apoM has recently been determined by X-ray crystallography, which revealed that h-apoM displays, as expected, a lipocalin-like fold characterized by an eight-stranded 13 barrel that encloses an internal fatty-acid-binding site. Surprisingly, this is not true for m-apoM. After refolding from inclusion bodies, the crystal structure of m-apoM (reported here at 2.5 angstrom resolution) displays a novel yet unprecedented seven-stranded beta-barrel structure. The fold difference is not caused by a mere deletion of a single beta-strand; instead, beta-strands E and F are removed and replaced by a single beta-strand A' formed from residues from the N-terminus. Molecular dynamics simulations suggest that m-apoM is able to adopt both a seven-stranded barrel structure and an eight-stranded barrel structure in solution, and that both folds are comparably stable. Thermal unfolding simulations identify the position where beta-strand exchange occurs as the weak point of the beta-barrel. We wonder whether the switch in topology could have a biological function and could facilitate ligand release, since it goes hand in hand with a narrowing of the barrel diameter. Possibly also, the observed conformation represents an on-pathway or off-pathway folding intermediate of apoM. The difference in fold topology is quite remarkable, and the fold promiscuity observed for m-apoM might possibly provide a glimpse at potential cross-points during the evolution of beta-barrels. (c) 2010 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1772477
- author
- Sevvana, Madhumati ; Kassler, Kristin ; Ahnström, Josefin LU ; Weiler, Sigrid ; Dahlbäck, Björn LU ; Sticht, Heinrich and Muller, Yves A.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- apolipoprotein, alternative conformations, misfolding, refolding, lipocalin
- in
- Journal of Molecular Biology
- volume
- 404
- issue
- 3
- pages
- 363 - 371
- publisher
- Elsevier
- external identifiers
-
- wos:000285372700002
- scopus:78349307798
- pmid:20932978
- ISSN
- 1089-8638
- DOI
- 10.1016/j.jmb.2010.09.062
- language
- English
- LU publication?
- yes
- id
- 80caf411-3364-460d-9ab2-21d0c8ca1f9d (old id 1772477)
- date added to LUP
- 2016-04-01 13:05:35
- date last changed
- 2022-01-27 17:17:39
@article{80caf411-3364-460d-9ab2-21d0c8ca1f9d,
abstract = {{Mouse apolipoprotein M (m-apoM) displays a 79% sequence identity to human apolipoprotein M (h-apoM). Both proteins are apolipoproteins associated with high-density lipoproteins, with similar anticipated biological functions. The structure of h-apoM has recently been determined by X-ray crystallography, which revealed that h-apoM displays, as expected, a lipocalin-like fold characterized by an eight-stranded 13 barrel that encloses an internal fatty-acid-binding site. Surprisingly, this is not true for m-apoM. After refolding from inclusion bodies, the crystal structure of m-apoM (reported here at 2.5 angstrom resolution) displays a novel yet unprecedented seven-stranded beta-barrel structure. The fold difference is not caused by a mere deletion of a single beta-strand; instead, beta-strands E and F are removed and replaced by a single beta-strand A' formed from residues from the N-terminus. Molecular dynamics simulations suggest that m-apoM is able to adopt both a seven-stranded barrel structure and an eight-stranded barrel structure in solution, and that both folds are comparably stable. Thermal unfolding simulations identify the position where beta-strand exchange occurs as the weak point of the beta-barrel. We wonder whether the switch in topology could have a biological function and could facilitate ligand release, since it goes hand in hand with a narrowing of the barrel diameter. Possibly also, the observed conformation represents an on-pathway or off-pathway folding intermediate of apoM. The difference in fold topology is quite remarkable, and the fold promiscuity observed for m-apoM might possibly provide a glimpse at potential cross-points during the evolution of beta-barrels. (c) 2010 Elsevier Ltd. All rights reserved.}},
author = {{Sevvana, Madhumati and Kassler, Kristin and Ahnström, Josefin and Weiler, Sigrid and Dahlbäck, Björn and Sticht, Heinrich and Muller, Yves A.}},
issn = {{1089-8638}},
keywords = {{apolipoprotein; alternative conformations; misfolding; refolding; lipocalin}},
language = {{eng}},
number = {{3}},
pages = {{363--371}},
publisher = {{Elsevier}},
series = {{Journal of Molecular Biology}},
title = {{Mouse ApoM Displays an Unprecedented Seven-Stranded Lipocalin Fold: Folding Decoy or Alternative Native Fold?}},
url = {{https://lup.lub.lu.se/search/files/3154443/1788795.pdf}},
doi = {{10.1016/j.jmb.2010.09.062}},
volume = {{404}},
year = {{2010}},
}