Why do different types of proteins exist

As we get to know them better we've thought we should have called disordered proteins, molecular rheostats. But to a physicist disorder just means thermal fluctuations are dominant, so for physicists it's an accurate description. The problem is that in the biomedical field the word disorder has been coopted for disease. You mention several tricks these proteins have up their sleeves. One I thought was clever was modulating the local chemical environment to encourage a particular reaction.

This is a very important idea. If you're doing chemistry in a test tube, and you want to make a reaction go, you increase the concentration of the reactants: A needs to bump into B and do so often. But this is a matter of probability so you might need a gazillion molecules of A and bazillion of B to get some statistics. But if there's a tether between A and B, they're guaranteed to bump into each other quite often.

You might be able to get away with a handful of molecules instead of gazillion. The loose tether, in effect, increases the concentration of A around B, and the tether is often a disordered region. Another thing you mentioned was cryptic disorder: the idea that structured proteins can become disordered.

That's such a backward flip. Richard Kriwacki of St. Jude Children's Research Hospital, a co-author of this perspective, is the person who made the clearest discovery in that regard. He shows that two structured domains can come together -- this is part of the whole p53 tumor suppressor apparatus -- and in trying to commingle, they undergo an unfolding transition that exposes sites that otherwise were buried.

This is the idea of cryptic disorder: that domains, by promoting disorder in one another, reveal hidden, or cryptic, motifs or sites that now are available for function. You mention that in the biomedical community disorder is associated with disease. Your co-author M. Cells make many decisions. They decide to differentiate, to die, to regenerate, or to go quiet ,and these decisions are controlled by regulatory networks.

The integrators in the networks are predominantly disordered regions. So the question is: Will mutations in those regions give rise to unwarranted cellular phenotypes and hence diseases, such as cardiovascular disorders, cancer and neurodegeneration? The answer is absolutely yes.

But what we are learning is that mutations in disordered regions don't necessarily generate a deleterious phenotype because disordered regions are fairly unconstrained compared to structured regions.

So these regions are also engines of robustness. At least the one study that looked at cancer mutation would suggest that. Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA. Phenylalanine hydroxylase. Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.

Growth hormone. These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. Other chapters in Help Me Understand Genetics. These include oxidation, deamidation, peptide-bond hydrolysis, disulfide-bond reshuffling and cross-linking. The methods used in the processing and the formulation of proteins, including any lyophilization step, must be carefully examined to prevent degradation and to increase the stability of the protein biopharmaceutical both in storage and during drug delivery.

The complexities of protein structure make the elucidation of a complete protein structure extremely difficult even with the most advanced analytical equipment. An amino acid analyzer can be used to determine which amino acids are present and the molar ratios of each. The sequence of the protein can then be analyzed by means of peptide mapping and the use of Edman degradation or mass spectroscopy. This process is routine for peptides and small proteins but becomes more complex for large multimeric proteins.

Peptide mapping generally entails treatment of the protein with different protease enzymes to chop up the sequence into smaller peptides at specific cleavage sites.

Two commonly used enzymes are trypsin and chymotrypsin. Mass spectroscopy has become an invaluable tool for the analysis of enzyme digested proteins, by means of peptide fingerprinting methods and database searching. Edman degradation involves the cleavage, separation and identification of one amino acid at a time from a short peptide, starting from the N-terminus.

One method used to characterize the secondary structure of a protein is circular dichroism spectroscopy CD. These spectra can be used to approximate the fraction of the entire protein made up of each type of structure. A more complete, high-resolution analysis of the three-dimensional structure of a protein is carried out using X-ray crystallography or nuclear magnetic resonance NMR analysis. To determine the three-dimensional structure of a protein by X-ray diffraction, a large, well-ordered single crystal is required.

X-ray diffraction allows measurement of the short distances between atoms and yields a three-dimensional electron density map, which can be used to build a model of the protein structure.

The use of NMR to determine the three-dimensional structure of a protein has some advantages over X-ray diffraction in that it can be carried out in solution and thus the protein is free of the constraints of the crystal lattice.

Many different techniques can be used to determine the stability of a protein. For the analysis of unfolding of a protein, spectroscopic methods such as fluorescence, UV, infrared and CD can be used. Thermodynamic methods such as differential scanning calorimetry DSC can be useful in determining the effect of temperature on protein stability. Enzymes are proteins, and they make a biochemical reaction more likely to proceed by lowering the activation energy of the reaction, thereby making these reactions proceed thousands or even millions of times faster than they would without a catalyst.

Enzymes are highly specific to their substrates. They bind these substrates at complementary areas on their surfaces, providing a snug fit that many scientists compare to a lock and key.

Enzymes work by binding one or more substrates, bringing them together so that a reaction can take place, and releasing them once the reaction is complete. In particular, when substrate binding occurs, enzymes undergo a conformational shift that orients or strains the substrates so that they are more reactive Figure 3.

The name of an enzyme usually refers to the type of biochemical reaction it catalyzes. For example, proteases break down proteins, and dehydrogenases oxidize a substrate by removing hydrogen atoms.

As a general rule, the "-ase" suffix identifies a protein as an enzyme, whereas the first part of an enzyme's name refers to the reaction that it catalyzes. Figure 3: Enzymes and activation energy Enzymes lower the activation energy necessary to transform a reactant into a product.

On the left is a reaction that is not catalyzed by an enzyme red , and on the right is one that is green. In the enzyme-catalyzed reaction, the enzyme binds to the reactant and facilitates its transformation into a product. Consequently, the enzyme-catalyzed reaction pathway has a smaller energy barrier activation energy to overcome before the reaction can proceed. The proteins in the plasma membrane typically help the cell interact with its environment.

For example, plasma membrane proteins carry out functions as diverse as ferrying nutrients across the plasma membrane, receiving chemical signals from outside the cell, translating chemical signals into intracellular action, and sometimes anchoring the cell in a particular location Figure 4. Figure 4: Examples of the action of transmembrane proteins Transporters carry a molecule such as glucose from one side of the plasma membrane to the other.

Receptors can bind an extracellular molecule triangle , and this activates an intracellular process. Enzymes in the membrane can do the same thing they do in the cytoplasm of a cell: transform a molecule into another form. Anchor proteins can physically link intracellular structures with extracellular structures. Figure Detail. The overall surfaces of membrane proteins are mosaics, with patches of hydrophobic amino acids where the proteins contact lipids in the membrane bilayer and patches of hydrophilic amino acids on the surfaces that extend into the water-based cytoplasm.

Many proteins can move within the plasma membrane through a process called membrane diffusion. This concept of membrane-bound proteins that can travel within the membrane is called the fluid-mosaic model of the cell membrane.

The portions of membrane proteins that extend beyond the lipid bilayer into the extracellular environment are also hydrophilic and are frequently modified by the addition of sugar molecules. Other proteins are associated with the membrane but not inserted into it.