Although the polypeptide chain is capable of great flexibility (see Figure 1), it also exhibits levels of defined folding, which are known as secondary and tertiary structures. Essential to the stability of these structures are noncovalent interactions between portions of the polypeptide chain. These interactions are summarized in Table 1. All are weaker than covalent bonds, with the hydrogen bond being the strongest. Electrostatic interactions between positive and negative charges on side chains can also be important. At physiological pH, arginines, lysines, and most histidines are positively charged, whereas aspartic and glutamic acids carry negative charges. Van der Waals interactions include a number of ways in which neutral molecules can attract one another, for example, via dipoles or charge fluctuations.
Fig1. Extended polypeptide chain showing typical backbone bond lengths and angles. Rn–2 , Rn–1 , and Rn represent different side chains. [Adapted from Petsko GA & Ringe D (2004) Protein Structure and Function. With permission from Oxford University Press.]
Table1. Molecular interactions determining protein secondary, tertiary, and quaternary structure.
The term secondary structure is reserved for regions of regular folding within the protein chain that are stabilized by hydrogen bonds between amide hydrogens and carbonyl oxygens in the polypeptide backbone. As described in Box 3.5, Linus Pauling proposed a number of possible secondary structures that both satisfied the planarity of the peptide group and allowed a maximum of hydrogen bonding. These have since been confirmed repeatedly in structures of real proteins. The most important secondary structures are the α-helix and β-sheet, as shown in Figure 2. In the α-helical conformation, hydrogen bonds are made between residues along the α-helix; in the β-sheet structure, hydrogen bonds are between parallel or antiparallel folds of the chain. The side chains of the residues do not play a direct role in forming these structures, but by steric effects they may favor one or the other. This can be made graphically clear in Ramachandran plots, as shown in Box 3.5.
Fig2. α-Helix and β-sheet: The two most common regular secondary structures in proteins. These structures differ mainly in how their stabilizing hydrogen bonds are formed. (A) In the α-helix, the hydrogen bonds are within a single length of coiled polypeptide chain and are oriented almost parallel to the helix axis. The number of residues in this helix is 3.6/ turn of the helix, which corresponds to 0.54 nm/turn. (B) In the β-sheet, the hydrogen bonds occur between spatially adjacent chains. These could belong to the same polypeptide chain folded back upon itself or to two individual chains of proteins that have multisubunit structures, as in quaternary structure. In the β-sheet, the hydrogen bonds are almost perpendicular with respect to the chain direction. [Illustration, Irving Geis. Image from the Irving Geis Collection, Howard Hughes Medical Institute, Chevy Chase, Maryland, USA. Rights owned by HHMI. Not to be reproduced without permission.]
