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Publication Abstract from PubMed

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 betabarrel 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 A 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.

Mouse ApoM displays an unprecedented seven-stranded lipocalin fold: folding decoy or alternative native fold?,Sevvana M, Kassler K, Ahnstrom J, Weiler S, Dahlback B, Sticht H, Muller YA J Mol Biol. 2010 Dec 3;404(3):363-71. Epub 2010 Oct 7. PMID:20932978^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.