Knowing the three-dimensional structure of a protein is an important part of understanding protein function, and structural biology often offers insights into molecular interactions. However, the protein structures we have examined so far are deceptively static. Proteins function by interacting dynamically with — binding to — other molecules. We divide these interactions into two types. In some interactions, the result is a reaction that alters the chemical configuration or composition of a bound molecule, with the protein acting as a reaction catalyst, or enzyme; we discuss enzymes and their properties in Chapter 6. In other interactions, neither the chemical configuration nor the composition of the bound molecule is changed; such interactions are the subject of this chapter.

It may seem counterintuitive that a protein’s interaction with another molecule could be important if it does not alter the associated molecule. Yet, transient interactions of this type are at the heart of many complex physiological processes, such as oxygen transport, transmission of nerve impulses, and immune function. Defining which molecules interact and quantifying such interactions are common and illuminating tasks in every biochemical subdiscipline.

The study of proteins that function through reversible interactions can be organized around six key principles of protein function, some of which will be familiar from Chapter 4:

• The functions of many proteins involve the reversible binding of other molecules. A molecule bound reversibly by a protein is called a ligand. A ligand may be any kind of molecule, including another protein. The transient nature of protein-ligand interactions is critical to life, allowing an organism to respond rapidly and reversibly to changing environmental and metabolic circumstances.

• A ligand binds a protein at a binding site that is complementary to the ligand in size, shape, charge, and hydrophobic or hydrophilic character. The interaction is specific: the protein can discriminate among the thousands of different molecules in its environment and selectively bind only one or a few types. A given protein may have separate binding sites for several different ligands. These specific molecular interactions are crucial in maintaining the high degree of order in a living system.

• Proteins are flexible. Changes in conformation may be subtle, reflecting molecular vibrations and small movements of amino acid residues throughout the protein. Changes in conformation may also be more dramatic, with major segments of the protein structure moving as much as several nanometers. Specific conformational changes are frequently essential to a protein’s function.

• The binding of a protein and a ligand is often coupled to a conformational change in the protein that makes the binding site more complementary to the ligand, permitting tighter binding. The structural adaptation that occurs between protein and ligand is called induced fit.

• In a multisubunit protein, a conformational change in one subunit often affects the conformation of other subunits.

• Interactions between ligands and proteins may be regulated.

The themes in our discussion of noncatalytic functions of proteins in this chapter — binding, specificity, and conformational change — are continued in Chapter 6, with the added element of proteins participating in chemical transformations. This discussion excludes the binding of water, which may interact weakly and nonspecifically with many parts of a protein.