2XKL

Crystal Structure of Mouse Apolipoprotein M

Summary for 2XKL

• Entry DOI: 10.2210/pdb2xkl/pdb
• Descriptor: APOLIPOPROTEIN M, GLYCEROL, N-PROPANOL, ... (6 entities in total)
• Functional Keywords: lipid transport
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Secreted (Potential): Q9Z1R3
• Total number of polymer chains: 1
• Total formula weight: 19338.94

Authors

Sevvana, M.,Kassler, K.,Josefin, A.,Weiler, S.,Dahlback, B.,Sticht, H.,Muller, Y.A. (deposition date: 2010-07-09, release date: 2010-10-13, Last modification date: 2024-11-13)

Primary citation

Sevvana, M.,Kassler, K.,Ahnstrom, J.,Weiler, S.,Dahlback, B.,Sticht, H.,Muller, Y.A.
Mouse Apom Displays an Unprecedented Seven-Stranded Lipocalin Fold: Folding Decoy or Alternative Native Fold?
J.Mol.Biol., 404:363-, 2010

PubMed 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 β‑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 Å resolution) displays a novel yet unprecedented seven-stranded β-barrel structure. The fold difference is not caused by a mere deletion of a single β-strand; instead, β-strands E and F are removed and replaced by a single β-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 β-strand exchange occurs as the weak point of the β-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 β-barrels.

PubMed: 20932978
DOI: 10.1016/J.JMB.2010.09.062

Experimental method

X-RAY DIFFRACTION (2.5 Å)