Membrane topology specifies the sidedness of a membrane-associated polypeptide chain: where its N-terminus, C-terminus and intervening protein domains lie relative to the lipid bilayer. Side-specific placement is essential to interpreting a cell-surface receptor.[ref]
Membrane Proteins. Molecular Biology of the Cell, 4th edition by Bruce Alberts and others; Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways: aqueous domains on either side and receptor orientation
For an original worked example, stipulate a continuous polypeptide chain with its N-terminus outside a biological cell, exactly three complete crossings of the cell membrane, and no additional excursions into the lipid bilayer. Its segments lie, in order, outside, inside, outside, inside. A protein domain between the first and second crossings faces the cytosol; one between the second and third faces the exterior; the C-terminus faces the cytosol. Counting crossings determines these placements without specifying an atomic protein structure.
The proof is a side-switching argument. Assign exterior the sign and interior . Each complete crossing multiplies the sign by , so after crossings,An odd number puts the termini on opposite sides, an even number on the same side. This assumes complete crossings of one boundary; a chain that enters and returns to the same side without crossing must not be counted as a complete crossing. Nor does the rule determine which side the N-terminus starts on.
As a constructed accessibility test, put an epitope on the outside segment between crossings two and three, and another on the inside segment between crossings one and two. Stipulate an intact cell membrane that excludes the test antibody and accessible epitopes that bind it. Applying the antibody outside can label only the first epitope. If both become accessible after opening the boundary, the difference tests sidedness under those assumptions. Failure to label an epitope alone is insufficient: it could also be inaccessible because of protein folding or poor antibody affinity. This is a proposed reasoning exercise, separate from the historical mixing experiment below.
Articles by others on the same topic
Membrane topology refers to the arrangement and orientation of proteins within a biological membrane, particularly in terms of how they span the lipid bilayer. It describes the number of transmembrane domains a protein has, their spatial arrangement, and which parts of the protein protrude into the cytoplasm, the extracellular environment, or the lumen of organelles.