• Question: Is the length of the polypeptide chain of a protein significant to such a degree? i.e, would it be possible to create a polypeptide chain of an enzyme that's significantly shorter than a naturally occuring one, yet have a similar active site, and hence, a similar effect? Or does the length of the polypeptide chain also account for more significant interactions rather than just an active site?

    Asked by dearlydie to Jo, Loren, Sam, Toby on 25 Jun 2014.
    • Photo: Tobias Warnecke

      Tobias Warnecke answered on 25 Jun 2014:


      Hi dearlydie,

      if you’re only interested in what happens in the active site, you can often chop off some parts of the protein and the main activity will still be there (although you need to leave enough of the chain so it can fold into a proper structure to make an active site). This is useful for biotechnology but in the cell, the proteins often need to do multiple things: for example, you might have a protein with an active site that also needs to bind to DNA or communicate with other proteins, so if you chop off bit of it, you might have a perfectly good active site, but compromise its other functions.

    • Photo: Jo Nettleship

      Jo Nettleship answered on 25 Jun 2014:


      Hi dearlydie,
      Yes you can do this, and scientists do this particularly in antibody work. You can make a polypeptide chain called an epitope which contain the parts of the antibody which bind to the antigen (thing which provokes the immune response). These are useful as you can make the epitopes synthetically.
      For the second half of your question, it depends on the protein in particular and its function. Some proteins only need the active site part in order to be active. However for others the shape is very important – for example an ion channel (a protein which allows salts to move through a cell membrane) uses its shape to move ions through the membrane.
      Jo

    • Photo: Loren Macdonald

      Loren Macdonald answered on 25 Jun 2014:


      Hi dearlydie,

      Interesting question there! In theory, yes, if the rest of the protein was not necessary for correct folding for the active site, then you could just create that part and it would work. Often it’s used the other way round, so you can use a small part of a protein that still folds properly to bind another protein and inhibit it’s action.

      Sometimes, however, the rest of the protein may be needed to have the protein in the right place in the cell or for it to interact with other things.

    • Photo: Sam Lear

      Sam Lear answered on 25 Jun 2014:


      To add to what has already been said – it is the shape of the protein that is important and there needs to be enough of the original chain there to fold into the required shape.

      In the case of cell signalling however (where cells send ‘messages’ using proteins in solution which interact with ‘receptor’ proteins on the surface of the membranes of other cells) the part of the sequence the you need of the message protein (‘ligand’) to have an effect can be very small.

      ‘Integrin’ receptors are a type of receptor that are activated by a number of relatively large ligands, which can be reduced to a chain of three amino acids (RGD – arginine/glycine/aspartic acid) that still has the same effect.

      Chemists can make molecules that are much smaller than proteins, but which bear this RGD sequence and can be used to change cell behaviour in the way the natural ligands do.

Comments