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- Cuviello, Flavia, et al.
(författare)
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Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6)
- 2015
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 589:24, s. 3921-3928
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Tidskriftsartikel (refereegranskat)abstract
- The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs. Two disease-causing mutations changing the number of positive charges in the loops of TMD0 did not affect the membrane insertion efficiencies of the adjacent TMs.
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- Monné, Magnus, 1973-
(författare)
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Transmembrane helices : tails, turns and snorkels
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The assembly and structure of membrane proteins are intimately related. Targeting and insertion of membrane proteins into the endoplasmatic reticulum (ER) membrane involve many components that facilitate the folding of the native structure. General rules for assembly mechanisms and structure determinants in the protein sequence, can be deduced from a number of techniques that are available to study membrane proteins.The focus of the thesis is on two aspects of membrane protein assembly: the membrane insertion of so-called N-tail proteins, and on how the overall length and the precise amino acid sequence of transmembrane helices (TMHs) affect their location and topology in the membrane. The work is largely based on the use of N-linked glycosylation, both as a topological marker and as a 'molecular ruler'.The first study demonstrates that the translocation of N-tails in eukaryotic polytopic membrane proteins can depend on downstream, synergistically acting TMHs. In the second study, the effect of charged residues on the location of a model TMH in the ER membrane was studied. The side-chains of positively charged residues were found to be able to 'snorkel' from a location within the hydrophobic core of the membrane up towards the lipid head-group region. Furhter studies on TMHs that are either too short or too long to fit the width of the ER membrane ('hydrophobic mismatch') suggest that short TMHs are positioned approximately perpendicular to the membrane, while long TMHs may compensate for their positive mismatch by bending. Finally, the formation of 'helical haipins', i.e., two TMHs connected by a tight turn, was studied by introducing each of the 20 naturally occurring amino acids near the middle of a very long hydrophobic segment. Charged residues and residues with high helix-breaking propensity were found to induce the formation of helical hairpins of which the shortest possible was found to consist of 31 hydrophobic residues including a turn promoting proline. A TMH turn propensity scale was derived, which hopefully can be used to improve current prediction programs for membrane protein topology.
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| 9. |
- Villarejo, Arsenio, et al.
(författare)
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Evidence for a protein transported through the secretory pathway en route to the higher plant chloroplast
- 2005
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Ingår i: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679. ; 7:12, s. 1224-1231
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to animal and fungal cells, green plant cells contain one or multiple chloroplasts, the organelle(s) in which photosynthetic reactions take place. Chloroplasts are believed to have originated from an endosymbiotic event and contain DNA that codes for some of their proteins. Most chloroplast proteins are encoded by the nuclear genome and imported with the help of sorting signals that are intrinsic parts of the polypeptides. Here, we show that a chloroplast-located protein in higher plants takes an alternative route through the secretory pathway, and becomes N-glycosylated before entering the chloroplast.
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