3 ms·

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

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.
f38zf5vdt 5y ago
Yes, many proteins have transitional global arrangements that it traverses as it meets some goal. For example, kinesin and dynein walk along microtubules in a way where we could never perfectly characterize the intermediary states since it's effectively a motor with free rotation around certain elements. A lot of crystallography is focused on enzymatic reactions where you bind a ligand that sits there for the sake of introducing some conformation that you can study. The ligands generally approximate the natural substrate at either the beginning, end, or some intermediate step in enzyme catalyzed synthesis.

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.

f38zf5vdt 5y ago

Yes, many proteins have transitional global arrangements that it traverses as it meets some goal. For example, kinesin and dynein walk along microtubules in a way where we could never perfectly characterize the intermediary states since it's effectively a motor with free rotation around certain elements. A lot of crystallography is focused on enzymatic reactions where you bind a ligand that sits there for the sake of introducing some conformation that you can study. The ligands generally approximate the natural substrate at either the beginning, end, or some intermediate step in enzyme catalyzed synthesis.