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Positive charge loading at protein termini is due to membrane protein topology, not a translational ramp


Reference:

Charneski, C. A. and Hurst, L. D., 2014. Positive charge loading at protein termini is due to membrane protein topology, not a translational ramp. Molecular Biology and Evolution, 31 (1), pp. 70-84.

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    Official URL:

    http://dx.doi.org/10.1093/molbev/mst169

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    Abstract

    In the great majority of genomes, the use of positive charge increases, on average, approaching protein N-termini. Such charged residues slow ribosomes by interacting with the negatively charged exit tunnel. This has been proposed to be selectively advantageous as it provides an elongation speed ramp at translational starts. Positive charges, however, are known to orientate proteins in membranes by the positive-inside rule whereby excess charge lies on the cytoplasmic side of the membrane. Which of these two models better explains the N-terminal loading of positively charged amino acids? We find strong evidence that the tendency for average positive charge use to increase at termini is exclusively due to membrane protein topology: 1) increasing N-terminal positive charge is not found in cytosolic proteins, but in transmembrane ones with cytosolic N-termini, with signal sequences contributing additional charge; 2) positive charge density at N-termini corresponds to the length of cytoplasmically exposed transmembrane tails, its usage increasing just up until the membrane; 3) membrane-related patterns are repeated at C-termini, where no ramp is expected; and 4) N-terminal positive charge patterns are no different from those seen internally in proteins in membrane-associated domains. The overall apparent increase in positive charge across all N-termini results from membrane proteins using positive charge adjacent to the cytosolic leaflet, combined with a skewed distribution of where N-termini cross the plasma membrane; 5) while Escherichia coli was predicted to have a 5′ ribosomal occupancy ramp of at least 31 codons, in contrast to what is seen in yeast, we find in ribosomal footprinting data no evidence for such a ramp. In sum, we find no need to invoke a translational ramp to explain the rising positive charge densities at N-termini. The membrane orientation model makes a full account of the trend.

    Details

    Item Type Articles
    CreatorsCharneski, C. A.and Hurst, L. D.
    DOI10.1093/molbev/mst169
    Related URLs
    URLURL Type
    http://www.scopus.com/inward/record.url?scp=84891816803&partnerID=8YFLogxKUNSPECIFIED
    DepartmentsFaculty of Science > Biology & Biochemistry
    Research CentresCentre for Mathematical Biology
    Publisher StatementPositive_charge_loading_at_protein_termini_is_due_to_membrane_protein_topology_not_a_translational_ramp_.pdf: This is a pre-copyedited, author-produced PDF of an article accepted for publication in MBE following peer review. The definitive publisher-authenticated version, Charneski, CA & Hurst, LD 2014, 'Positive charge loading at protein termini is due to membrane protein topology, not a translational ramp' Molecular Biology and Evolution, vol 31, no. 1, pp. 70-84., is available online at http://dx.doi.org/10.1093/molbev/mst169.
    RefereedYes
    StatusPublished
    ID Code38385

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