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>proteins with less defined structures are generally harder to solve with the usual methods like X-ray crystallography What do you mean by 'proteins with less

• fabian2k 5y ago
  Less defined means flexible in this case. So either parts that are completely random on their own, or parts that can adopt multiple different structures. There are also intrinsically disordered proteins that have no defined structure when they are on their own, that's essentially like a piece of string that is almost completely flexible. Those proteins can still adopt a specific well-defined structure if they bind to something else.
  • alan-hn 5y ago
    So does flexible mean that there may be different amino acids in a portion of the peptide? From my understanding, when flexibility is discussed in terms of proteins we're talking about rigid vs flexible side chains which can move or rotate along specific bonds So for the intrinsically disordered ones, are you mainly talking about the secondary or tertiary structures? My assumption based on your statement is that we're keeping the same primary structure (order of amino acids) but they don't have many (if any at all) intermolecular interactions? Would it be safe to assume that you're referring to shorter polypeptide rather than large proteins?
    • dekhn 5y ago
      in disordered proteins, there is no permanent tertiary structure. they may have some secondary structure, but the relations of those structural elements can change in time. It does not mean the seuqence has variation in it.
      • alan-hn 5y ago
        Does this mean that they have multiple conformational states with similar energies that are easy for it to transition between? How different are the states and is this how the protein normally does its proteiny stuff?
        • dekhn 5y ago
          yes, I would say that intrisnically disordered proteins adopt something like an unfolded state, which is to say that they can visit a wide range of structures that are at similar energy levels, all of which are accessible at ~room temp. I can't really answer in more detail because all the ID proteins are fairly different an dhow they do their job is hard to understand compared to stable static "rocks" like enzyymes.
          • throwawaybio3 5y ago
            Enzymes aren't stable and static -- usually in their active site they have significant conformational changes that enable catalysis of the relevant chemical reaction. It's quite a problem that we don't have general robust ways of directly elucidating those transient structures, a lot of our understanding of catalysis is still held back or slow-evolving because we can only use indirect and cumbersome methods (like isotopic mutation + laser IR) I would consider most enzymes to be intrinsically disordered at their active sites.
            • dekhn 5y ago
              No enzymes are not intrinsically disordered at their active sites. They are highly ordered. Most enzymes don't undergo large changes- they accept a molecule, do their business, and release it. You're thinking of other proteins like motor proteins which under go large, controlled conformational changes. The active site is structured to stabilize the transition state of the affected molecule and move it from one state to the next in the chemical reaction. That requires very specific shapes and correlated changes. But of course, this being biology, you can remove all 3 active site residues in a serine protease catalytic triad, and still see proteolysis because the protein, when it binds the substrate, forces the subtrate into its transition pathway. People have been working on these things for quite some time- I saw talks about time-resolved crystallography of active sites, and while they say "significant structure changes", they really only mean localized breathing-like motions, not massive rotations of entire domains.
• dekhn 5y ago
  think loose floppy piles of spaghetti instead of well-defined rocks.
• tintor 5y ago
  Example by analogy: Flat tire has less defined structure, and can take many shapes. Inflated tire has more defined structure, and behaves more predictably.
• jostmey 5y ago
  The same protein can deform into multiple different 3D shapes, called conformations. Some proteins are rigid and exist almost exclusively in a single conformation. It is probably easier to determine the 3D structure of proteins with a single, dominant conformation. Other proteins don't have well defined conformations, and are more like a tangle of rope that can bend in many different ways
  • panabee 5y ago
    thanks for the explanation. what are the biggest factors influencing conformation? what are the best ways today for imaging proteins with different conformations, and what are the limitations of these methods?
• abcc8 5y ago
  Many proteins have intrinsically disordered regions that are hypothesized to be directly related to the protein's role in the cell. These regions are termed disordered because current methods used to determine the structure of proteins are unable to resolve a regular structure for these regions in the context of a protein crystal or protein in solution. This publication is an informative review on the topic: https://pubs.acs.org/doi/10.1021/cr400525m https://pubs.acs.org/doi/10.1021/cr400525m