Protein Secondary Structure

Transcription

1 Protein Secondary Structure Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 2, pp Problems in textbook: chapter 2, pp , #1,5,9 Directory of Jmol structures of proteins: Basic Jmol structure of the helix: Jmol routine showing lots of views of helix & 2 other kinds of helices: Jmol structures of some -helical proteins Jmol structures of barrel and clam proteins 1

2 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 3 10 helix (not covered in this course) Secondary structures are stabilized by all kinds of 2 noncovalent bonds, but especially by hydrogen bonds.

3 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. protein backbone amide groups (amide C=O: ---- H N) 3

4 Review: 4 successive planar peptide groups bounded by the C s of 5 successive amino acid residues 6 coplanar atoms of 1 peptide bond: C α(n) CO NH C α(n+1) from C of one residue to a C of next residue) Peptide animation: Secondary structures stabilized mainly by hydrogen bonds between backbone amide N H groups and carbonyl O: s 4

5 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. Berg et al., Fig

6 helix Animations: 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. Whole helix a dipole: - each peptide bond has dipole moment - dipole moments are vectors, so they sum to make a net dipole for the helix N-term end + C-term end (N)( +) N I H C O II 3.6 residues This is best seen in the ball and stick diagram on previous slide (C)( ) 6

7 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.) Berg et al. Fig

8 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

9 Proteins with a lot of the polypeptide chain in -helical conformation Jmol structures of some -helical proteins Examples: Ferritin (an iron storage protein) Berg et al., Fig Myoglobin (O 2 -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

10 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

11 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

12 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

13 conformation Parallel conformation (strands run in same direction) Berg et al., Fig Mixed conformation (mixture of parallel and antiparallel strands) Berg et al., Fig

14 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

15 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

16 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 Principles of Biochemistry, 16 3rd ed., Fig. 4-7a

17 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 Principles of Biochemistry, 17 3rd ed., Fig. 4-7b

18 Examples of conformation in proteins Jmol structures of barrel and clam proteins twisted sheet (A: ball & stick; B: ribbon model; C: ribbon model from "side" to show "twist") (Berg et al., Fig. 2-39) Berg et al., Fig

19 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) Berg et al., Fig

20 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) Berg et al., Fig

21 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). Berg et al., Fig

22 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

23 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

24 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