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Protein Secondary Structure Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 2, pp. 37-45 Problems in textbook: chapter 2, pp. 63-64, #1,5,9 Directory of Jmol structures of proteins: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/routines/routines.html Basic Jmol structure of the helix: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha/alpha.html Jmol routine showing lots of views of helix & 2 other kinds of helices: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/helices/helices.html Jmol structures of some -helical proteins http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha_domain/alpha_domain.html Jmol structures of barrel and clam proteins http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/beta_domain/beta_domain.html 1 Key Concepts • Proteins: secondary structure – major types of secondary structure found in many proteins: helix conformation turns – surface loops: not really secondary structure because not regular, repetitive – Unusual secondary structures - examples: • collagen helix (found in collagen) (not covered in this course) • other kinds of helices, e.g. pi helix and 310 helix (not covered in this course) • Secondary structures are stabilized by all kinds of 2 noncovalent bonds, but especially by hydrogen bonds. Protein Secondary Structure • Local, regular/recognizable conformations observed for parts of the peptide backbone of a protein • Examples: – helix conformation turns collagen helix • Properties of peptide bond & hydrogen bonds --> 2° structures –peptide bonds • planarity • adjacent planes related in space by set of 2 dihedral angles for each amino acid residue –hydrogen bonds • Strongest are linear. • Protein functional groups capable of H-bonding tend to do so to maximum possible extent. 3 • protein backbone amide groups (amide C=O: ---- H–N) Review: 4 successive planar peptide groups bounded by the C’s of 5 successive amino acid residues •6 coplanar atoms of 1 peptide bond: Cα(n)–CO–NH– Cα(n+1)from C of one residue to a C of next residue) •Peptide animation: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/peptide/peptice.html •Secondary structures stabilized mainly by hydrogen bonds between backbone amide N–H groups and carbonyl O:’s 4 helix • • • • backbone coiled (spiral) conformation -- rod-like structure Usually right-handed in proteins R groups radiate outward from helical “cylinder” Backbone -- regular, repeating rotation, residue by residue: Each residue has close to the same ( ,) coordinates. 5 Berg et al., Fig. 2-29 • helix Animations: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha/alpha.html http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/helices/helices.html • • Hydrogen bonding pattern for helix: H bonds almost parallel to helix axis, from carbonyl O: of residue n to H–N group of residue (n+4). 3.6 residues per 360° turn of helix. (N)(+) •Whole helix a dipole: - each peptide bond has dipole moment - dipole moments are vectors, so they sum to make a net C dipole for the helix •N-term end + •C-term end – 3.6 residues N I H O II This is best seen in the ball and stick diagram on previous slide (C)(–) 6 Ramachandran Plot, (, ) angles for helix • For regular, repeating local structures like helix, each residue has ~ the same (,) angles. ( conformation has a different set of (,) values.) 7 Berg et al. Fig. 2-31 What terminates an -helix? Statistically, a very high percentage (~60%) of helices are terminated by a single amino acid, Proline: The formation of the cyclic structure between the 3 C R-group and the -N results eliminates free rotation around the -bond. Proline is sometimes called the helix “breaker”. 8 Proteins with a lot of the polypeptide chain in -helical conformation • Jmol structures of some -helical proteins http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha_domain/alpha_domain.html Examples: Ferritin (an iron storage protein) Berg et al., Fig. 2-33 Myoglobin (O2-binding protein especially rich in muscle cells) <–– space-filling atoms (all non-H atoms shown) Ribbon rendition ––> shows only the polypeptide backbone tracing in space Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig. 4-16 9 Coiled coils of helices in some proteins • 2 right-handed -helices coiled around each other in left-handed direction • Supercoiled structure has great tensile strength (like a rope with twisted strands). • Examples: - -keratin (a fibrous protein -- elongated 3-dimensional structure, waterinsoluble) -- mammalian hair, quills, claws, horns – Some globular proteins (compact 3-D structure) -- examples: • Some transcriptional regulator proteins (“leucine zipper” motif) • Myosin (muscle) Berg et al., Fig. 2-43 10 conformation • Backbone nearly fully extended (not coiled) • All residues in -sheet have ~ the same (f,y) angles • Distance between adjacent AA residues ~3.5 Å (further apart, more stretched out, than in -helix) • Side chains (R groups) point in alternate/opposite directions for adjacent residues in chain • N-H group and C=O group of peptide bond point in opposite directions, away from average direction of extended backbone of chain Berg et al., Fig. 2-35 11 conformation • Backbone amide N-H and C=O groups again almost fully hydrogen-bonded, but hydrogen bonds can be between different sections of the backbone OR between sections of backbone on different polypeptide chains. • No predictable relationship in the amino acid sequence for what sections are hydrogen bonded to each other • Hydrogen bonds more or less at right angles to direction of backbone of chain Antiparallel conformation (strands run in opposite directions) Berg et al., Fig. 2-36 12 conformation Parallel conformation (strands run in same direction) Berg et al., Fig. 2-37 Mixed conformation (mixture of parallel and antiparallel strands) Berg et al., Fig. 2-38 13 Ramachandran Plot: (, ) angles for conformation • For regular, repeating local structures like helix or for conformation, each residue has ~ the same (,) angles. ( conformation has its own set of (,) values, different from helix.) Left-handed alpha helix Right-handed alpha helix 14 Berg et al. Fig. 2-34 pleated sheets • 4-stranded antiparallel β pleated sheet • planes of peptide bonds ("pleats") indicated • R groups (yellow) alternately extending above and below sheet. Garrett & Grisham, Biochemistry, 3rd ed., Fig. 6-10 15 pleated sheets • 3-stranded antiparallel β pleated sheet • planes of peptide bonds ("pleats") indicated • R groups (purple) alternately extending above and below sheet. Nelson & Cox, Lehninger 16 Principles of Biochemistry, 3rd ed., Fig. 4-7a pleated sheets • 3-stranded parallel β pleated sheet • planes of peptide bonds ("pleats") indicated • R groups (purple) alternately extending above and below sheet. Nelson & Cox, Lehninger 17 Principles of Biochemistry, 3rd ed., Fig. 4-7b Examples of conformation in proteins • Jmol structures of barrel and clam proteins http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/beta_domain/beta_domain.html • twisted sheet (A: ball & stick; B: ribbon model; C: ribbon model from "side" to show "twist") (Berg et al., Fig. 2-39) 18 Berg et al., Fig. 2-39 Examples of conformation in proteins • Fatty acid binding protein (mostly conformation; sheet in a “clam” motif • Green fluorescent protein ( barrel structure; used as a “reporter” in molecular genetics experiments) 19 Berg et al., Fig. 2-40 turns (reverse turns, hairpins, bends) • Abrupt change in direction of polypeptide backbone, at surface of protein • Stabilized by hydrogen bond across “stem” of hairpin • Sharp turn in space --> steric problems with larger amino acid side chains – often involve Gly, Asn, Ser (small hydrophilic residues) or – Pro (has “built-in” elbow/bend in backbone to help start turn) 20 Berg et al., Fig. 2-41 “Loops” (not really “secondary structure”) • • • • No regular, recognizable or periodic structures Longer “excursions” of backbone than simple reverse turns Usually at surface of protein Often mediate interactions with other molecules • Example: loops in antibodies • Figure shows structure of one domain of an antibody polypeptide (red loops involved in binding antigen; flexible structures in loops interact with antigen). 21 Berg et al., Fig. 2-42 Up next: • Tertiary structure: 3-dimensional conformation of whole polypeptide in its folded state • Quaternary structure: 3-dimensional relationship of the different polypeptide chains (subunits) in a multimeric protein; the way the subunits fit together and their symmetry relationships – Only in proteins with more than one polypeptide chain – Proteins with only one chain have no quaternary structure. 22 Learning Objectives • Define secondary structure. • List examples of categories of secondary structure that occur in proteins. • Describe the -helix, including what groups serve as hydrogen bond donors and acceptors, chirality of most helices in proteins (right- or left-handedness), number of residues per turn, orientation of R groups relative to axis of the helix, the helix dipole (which end is +, which is –), and packing density of atoms. • Describe -conformation, including which groups serve as hydrogen bond donors and acceptors, and orientation of R groups in a pleated sheet. • Explain parallel and antiparallel conformation. 23 Learning Objectives, continued • Identify the most important noncovalent interactions stabilizing the -helix and -conformations. • Explain what a -turn is, where -turns are often found in proteins, and what types of amino acid residues are often found in -turns. • Be able to identify -helices and -strands (or sheets consisting of 2 or more -strands) on a ribbon depiction of a protein structure. 24