BS2520 - Protein Structure and Function Lecture 4 Protein Folding Overview of protein structural hierarchy: - Traditional classification - primary, secondary, tertiary, quaternary. - Motifs. - Domains. - Relevant resources. Motifs Specific geometric arrangements of individual secondary structure elements referred to as motifs. Motifs comprise a part of the larger structural assembly, they can be associated with a specific function. Helix-Turn-Helix: - This motif is found in many proteins. N C "helix-turn-helix": EF Hand: - All DNA polymerases are structurally similar - finger and thumb domains wrap around DNA and hold it across the enzymes active site = palm domain. - DNA polymerases require a metal ion for activity. N B A C D C E F Hairpin B: - Two adjacent anti-parallel strands joined by a loop. - Found in most anti-parallel ß structures (forming ribbons and more complex sheets). - The most stable confirmation is when two ß strands are adjacent in both primary sequence and structure. - The length of the loop varies but is most commonly 2-5 amino acids long. Hairpin Greek Key: - This structure resembles a fret - repeating unit of ornamental pattern, but it is not associated with any function. - Likely folding pattern due to foldings of long antiparallel ß strands. C NY C. hairpin ? motif: the simplest motif (arrows represent ß strands) folding
Two adjacent hairpin motifs can be arranged into a B-sheet in 24 different ways - topological arrangements. Antiparallel B-sheets are the most diverse group of structures. Two sheets are stabilised by proteins inside being packed against each other to form parrel like structures. ?-?-?: - Forms crossover connections to connect two parallel ß strands, must have two loop regions. - Function - shield hydrophobic residues of ß-sheets from solvents. - They can be left-handed or right-handed. ?-?-? motif (top left): cylinders represent a helices arrows represent ß strands Other commonly occurring protein motifs: - Zn finger motifs - 1 a and 2 ß strands with antiparallel orientations. - Coiled coil motifs - a helices where the hydrophobic amino acids wind together forming a coil. Domains Motifs are combinations of a few secondary structure elements which occur frequently, simple motifs are arranged into complex motifs which form domains. Domains are a fundamental unit of tertiary structure: - A compact folding region in a polypeptide of 100-150 amino acids. - Self-forming, self-stabilising. - Has a tertiary structure consisting of weak non-covalent interactions, a hydrophobic interior and hydrophilic exterior, H-bonds and S-S bridges. Proteins can have 1 or more domainstt structurally similar domains may be associated with similar or different functions. Domains can be classified into three main structural groups: - a structures where the core is built exclusively from a-helices. - B structures comprise of antiparallel ß-sheets. - a/B structures are a combination of B-a-ß motifs form predominantly parallel ß-sheets surrounded by a-helices. - a + B structures are built from a combination of discrete a and B motifs packed against each other. - A special group comprising mostly