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Molecular chaperones help shape proteins

Within a living cell, a polypeptide chain is sometimes in danger of binding the wrong substance. There are two major situations when this can occur:

  1. Just after a protein is made. When a protein has not yet folded completely, it can present a surface that binds the wrong molecule.

  2. Following denaturation. Certain conditions, such as moderate heat, can cause some proteins in a living cell to denature without killing the organism. Before the protein can refold, it may present a surface that binds the wrong molecule. In these cases, the inappropriate binding may be irreversible.

Many cells have a special class of proteins, called chaperones, that protect the three-dimensional structures of other proteins. They bind to their partner proteins just as they are being made and also when they become denatured. Like the chaperones at a high school dance, chaperone proteins prevent inappropriate interactions and enhance appropriate ones. Typically, a chaperone protein has a cagelike structure that pulls in a polypeptide, causes it to fold into the correct shape, and then releases it (Figure 3.14). Tumors make chaperone proteins, possibly to stabilize proteins important in the cancer process, and so chaperone-inhibiting drugs are being designed for use in chemotherapy. In some clinical situations, treatment with these inhibitors results in the inappropriate folding of proteins in tumor cells, causing the tumors to stop growing.

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Figure 3.14 Molecular Chaperones Protect Proteins from Inappropriate Binding Chaperone proteins surround new or denatured proteins and prevent them from binding to the wrong substances. Heat shock proteins such as HSP60, shown here, make up one class of chaperone proteins.

Q: Why are heat shock proteins important for a cell?

Heat shock proteins protect cellular proteins from being denatured and possibly broken down. This can occur not only when proteins are exposed to heat, but in any chemical situation where their structure is altered (e.g., a change in pH).