6ew2

Human myelin protein P2 F57A mutant, tetragonal crystal form

spinqualitylabelsall models 6ew2, resolution 1.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ew2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.588Å Ligands: CL, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYP2_HUMAN May play a role in lipid transport protein in Schwann cells. May bind cholesterol. Publication Abstract from PubMed BACKGROUND: Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been proposed to participate in membrane and fatty acid binding and conformational changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the opening of the portal region upon ligand entry and egress. RESULTS: We performed a structural characterization of the F57A mutant of human P2. The mutant protein was crystallized in three crystal forms, all of which showed changes in the portal region and helix alpha2. In addition, the behaviour of the mutant protein upon lipid bilayer binding suggested more unfolding than previously observed for wild-type P2. On the other hand, membrane binding rendered F57A heat-stable, similarly to wild-type P2. Atomistic molecular dynamics simulations showed opening of the side of the discontinuous beta barrel, giving important indications on the mechanism of portal region opening and ligand entry into FABPs. The results suggest a central role for Phe57 in regulating the opening of the portal region in human P2 and other FABPs, and the F57A mutation disturbs dynamic cross-correlation networks in the portal region of P2. CONCLUSIONS: Overall, the F57A variant presents similar properties to the P2 patient mutations recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a residue regulating conformational changes that may accompany membrane surface binding and ligand exchange in P2 and other FABPs. Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the beta barrel in fatty acid binding proteins.,Laulumaa S, Nieminen T, Raasakka A, Krokengen OC, Safaryan A, Hallin EI, Brysbaert G, Lensink MF, Ruskamo S, Vattulainen I, Kursula P BMC Struct Biol. 2018 Jun 25;18(1):8. doi: 10.1186/s12900-018-0087-2. PMID:29940944 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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