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Intracellular protein topogenesis.

G Blobel

    Proceedings of the National Academy of Sciences of the United States of America
    |March 1, 1980
    PubMed
    Summary
    This summary is machine-generated.

    Proteins use specific "topogenic" sequences to cross membranes and reach their destinations. These sequences guide protein translocation and integration, ensuring correct cellular organization.

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    Area of Science:

    • Molecular Biology
    • Cell Biology
    • Biochemistry

    Background:

    • Proteins are synthesized on ribosomes and must be correctly localized within or across cellular membranes.
    • Post-synthesis, proteins require sorting for export or targeting to specific intracellular compartments.
    • The precise mechanisms governing protein localization and membrane integration are complex.

    Purpose of the Study:

    • To propose a unifying hypothesis for protein topogenesis, the process of protein localization and membrane integration.
    • To identify and categorize the discrete "topogenic" sequences responsible for directing protein traffic.
    • To elucidate how these sequences are decoded by cellular effectors.

    Main Methods:

    • Theoretical analysis of protein translocation and membrane integration mechanisms.

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  • Classification of topogenic sequences based on their proposed functions (signal, stop-transfer, sorting, insertion).
  • Review and synthesis of existing experimental evidence for protein targeting.

    • Main Results:

    • Hypothesized that "topogenic" sequences within polypeptide chains encode protein localization information.
    • Identified four distinct types of topogenic sequences: signal, stop-transfer, sorting, and insertion sequences.
    • Proposed that a limited repertoire of topogenic sequences accounts for the topological equivalence of many proteins.

    Conclusions:

    • Topogenic sequences provide the necessary information for unidirectional translocation, asymmetric integration, and sorting of proteins across cellular membranes.
    • These sequences are decoded by specific cellular effectors, such as protein translocators.
    • The proposed model offers a framework for understanding protein topogenesis and its evolutionary implications for cellular organization.