Last updated on November 19, 2018 at 17:16
- Proteins need to be folded into their correct structure to be active. Sometimes, proteins cannot do this on their own, but need chaperones to help them.
- The proteins primary structure, their amino acid sequence, is what determines their 3d structure.
- Several agents can disrupt the bonds that stabilize proteins 3d structure, for example urea, pH extremes and DTT
- Molecular chaperones catalyse the correct folding of proteins, but are not part of the product
- During periods of cellular stress, the probability of proteins folding wrongly is higher. Therefore, cellular stress, like heat, induces expression of certain chaperones called Heat shock proteins, that make sure that proteins aren’t folded incorrectly.
- The GroEL/GroES complex is an important chaperonin.
To understand protein folding, we need to remember thermodynamics. Molecules always want to have as little free energy as possible. The less free energy a molecule has, the more stable it is. Proteins are correctly folded when they are in a conformation that contains as little free energy as possible. Because a folded protein contains less free energy than an unfolded protein, protein folding is a spontaneous process. However, the proteins might still need help sometimes.
Consider the picture on the right. The protein starts at the top of the canyon, when it is an unfolded polypeptide chain and contains a lot of free energy. When it begins to fold by itself, it will lose some of this free energy, become more stable, and fall down the canyon. However, the protein might get stuck at some places. Let’s say the protein starts to fold, but gets “stuck” where the blue arrow points. The protein still contains a lot of free energy (it’s only halfway to the bottom!), but it cannot continue to fold, because of the little “energy peak” that the red arrow points to. The protein needs a little energy “push” to get over this peak, to continue folding correctly to finally fold into its native, active structure. This “push” can be provided by chaperones.
Another example you can use to imagine why proteins fold, is to look at your hand. To stretch it open to a flat hand, you need to use some energy. If you let go, the hand will spontaneously “fold” because this “folded” state is the one that requires the least energy.
Molecular chaperones are molecules that catalyse the correct folding of proteins. Some chaperones are always present in the cell, while some are expressed only in response to cellular stress. During cellular stress, like heat, proteins have a higher tendency to fold incorrectly. In these cases, chaperones are even more needed than usual. That’s why cellular stress increases expression of chaperones called Heat shock proteins. Chaperonins are a class of chaperones that produce favourable conditions for proteins to fold correctly. The best-known is the GroEL/GroES complex, which needs uses ATP. Misfolded proteins cause Parkinson’s, Alzheimer’s and Huntington’s.
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