1 September, 2004 Chapter 5 Macromolecular Structure

Overview DNA structure is stabilized by base pairing, base stacking (  interactions and hydrophobic interactions) and hydrogen bonding to water. Protein structure is determined by the sequence of amino acids in the polymer. Bond-rotation and hindrance constraints of different amino acids determine which secondary structures are available for a given primary sequence. Hydrogen bonds and hydrophobic interactions determine tertiary structure. Most proteins are modular: composed of multiple domains. Weak bonds position proteins at specific DNA binding sites. Allosteric events regulate protein activity.

DNA Structure A-T and G-C base pairs hold the strands of the double helix together. Base stacking (  interactions and hydrophobic interactions) and hydrogen bonding to water also stabilize the double helix. Many weak bonds make a very stable structure. DNA unwinding is gradual.

RNA Structure The single-stranded nature of RNA allows unique secondary structures, including stem-loops, and metal-stabilized structures. Base stacking is critical in RNA structures.

Protein Structure Amino acids are diverse compared to nucleotide monomers.

Peptide bonds have partial double-bond character, and are planar. Protein folding is constrained by phi and psi rotation about the bonds adjacent to the alpha carbon.

Alpha Helices Alpha helices are regular structures, with precise requirements for phi and psi. Side chains project away from the helix core. Proline cannot adopt this conformation. Glycine, Tyrosine and Serine are also rare in helices. Protein structure prediction from sequence is complicated.

Beta Sheets Beta sheets are extended structures stabilized by hydrogen bonding between carbonyl and amino groups of adjacent strands. Side chains project above and below the plane of the sheet.

Beta Sheets Beta may be parallel or antiparallel.

Beta Sheets Beta sheets tend to twist.

Polypeptide chains fold into complex shapes. Regions of regular and irregular structure. Stabilized by hydrogen bonds and hydrophobic interactions.

Coiled Coil Interactions

Domain Structure Domains are structurally and functionally distinct parts of proteins.

Domain Structure Biochemically similar proteins often have similar domains.

Intermolecular interactions Weak bonds also specify which interactions are possible between molecules, including DNA-protein interactions.  -helix is a good fir for the major grove, where hydrogen bonding can be used to recognize a specific sequence. Dipole moment of the helix allows interactions with DNA backbone.

Intermolecular interactions Non-specific interactions target binding proteins to DNA, allowing for a two-dimensional diffusion, speeding recognition.

Allosteric Regulation Changes in protein shapes modulate activity.