secondary structure of proteins : sheets supersecondary structure
DESCRIPTION
Secondary structure of proteins : sheets supersecondary structure. Levels of protein structure organization. Peptide bond geometry. Hybrid of two canonical structures. 60%40%. Dihedrals with which to describe polypeptide geometry. side chain. main chain. - PowerPoint PPT PresentationTRANSCRIPT
SECONDARY STRUCTURE OF PROTEINS: HELICES, SHEETS,
SUPERSECONDARY STRUCTURE
Levels of protein structure organization
60% 40%
Hybrid of two canonical structures
Peptide bond geometry
Dihedrals with which to describe polypeptide geometry
main chain
side chain
Because of peptide group planarity, main chain conformation is effectively defined by the and angles.
The Ramachandran map
Conformations of a terminally-blocked amino-acid residue
C7eq
C7ax
E Zimmerman, Pottle, Nemethy, Scheraga, Macromolecules, 10, 1-9 (1977)
A Ramachandran plot for BPTI
(M6.10)
Energy maps of Ac-Ala-NHMe and Ac-Gly-AHMe obtained with the ECEPP/2 force field
Energy curve of Ac-Pro-NHMe obtained with the ECEPP/2 force field
L-Pro-68o
Dominant -turns
Types of -turns in proteins
Hutchinson and Thornton, Protein Sci., 3, 2207-2216 (1994)
Older classification
Lewis, Momany, Scheraga, Biochim. Biophys. Acta, 303, 211-229 (1973)
i+1=-60o, i+1=-30o, i+2=-90o, i+2=0o i+1=60o, i+1=30o, i+2=90o, i+2=0o
i+1=-60o, i+1=-30o, i+2=-60o, i+2=-30o i+1=60o, i+1=30o, i+2=60o, i+2=30o
i+1=-60o, i+1=120o, i+2=80o, i+1=0o i+1=60o, i+1=-120o, i+2=-80o, i+1=0o
i+1=-80o, i+1=80o, i+2=80o, i+2=-80o
i+1|80o, |i+2|<60o
i+1|60o, |i+2|180o
cis-proline
Hydrogen bond geometry in -turns
Average for -turns-turn
Asx-type -turns
Type of structure
Helical structures
-helical structure predicted by L. Pauling; the name was given after classification of X-ray diagrams.
Helices do have handedness.
Average parameters of helical structures
TypeH-bond Size of the
ring closed by the H-bond
radius
Geometrical parameters of helices
Idealized hydrogen-bonded helical structures: 310-helix (left), -helix (middle), -helix (right)
Criterion for hydrogen bonding: the DSSP formula
qN=qO=-0.42 e ; qH=qC=+0.20 e
Kabsch W, Sander C (1983). "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features". Biopolymers 22 (12): 2577–637
Define Secondary Structure of Proteins
Schematic representation -helices: helical wheel
3.6 residues per turn = a residue every 100o.
Examples of helical wheels
Amphipatic (or amphiphilic) helices
Hydrophobic
Hydrophilic
hydrophilic head groupaliphatic carbon chain lipid
bilayer
Amphipatic helices often interact with lipid membranes
One side contains hydrophobic amino-acids, the other one hydrophilic ones.
In globular proteins, the hydrophilic side is exposed to the solvent and the hydrophobic side is packed against the inside of the globule
download cytochrome B562
Length of -helices in proteins
10-17 amino acids on average (3-5 turns); however much longer helices occur in muscle proteins (myosin, actin)
Proline helices (without H-bonds)
Polyproline helices I, II, and III (PI, PII, and PIII): contain proline and glycine residues and are left-handed.
PII is the building block of collagen; has also been postulated as the conformation of polypeptide chains at initial folding stages.
Structure residues/turn translation/residue
-helix -57 -47 180 +3.6 1.5
310-helix -49 -26 180 +3.0 2.0
-helix -57 -70 180 +4.4 1.15
Polyproline I -83 +158 0 +3.33 1.9
Polyproline II -78 +149 180 -3.0 3.12
Polyproline III -80 +150 180 +3.0 3.1
The, and angles of regular and polyproline helices
Poly-L-proline in PPII conformation, viewed parallel to the helix axis, presented as sticks, without H-atoms. (PDB)It can be seen, that the PPII helix has a 3-fold symmetry, and every 4th residue is in the same position (at a distance of 9.3 Å from each other).
Deca-glycine in PPII and PPI without hydrogen atoms, spacefill modells, CPK colouring
PPI-PRO.PDB
PPII-PRO.PDB
The -helix
Comparison of -helical and -sheet structure
-sheet structures
Alpha, Beta, … I got ALL the letters up here, baby!
Pauling and Corey continued thinking about periodic structures that could satisfy the hydrogen bonding potential of the peptide backbone. They proposed that two extended peptide chains could bond together through alternating hydrogen bonds.
A single -strand
An example of-sheet
Antiparallel sheet (L6-7)
The side chains have alternating arrangement; usually hydrophobic on one and hydrophilic on the opposite siteresulting in a bilayer
2TRX.PDB
Parallel sheet (L6-7)
The amino acid R groups face up & down from a beta sheet
2TRX.PDB
Structure Residues/turn Translation/residue
Antiparallel -139 +135 -178 2.0 3.4
Parallel -119 +113 180 2.0 3.2
-helix -57 -47 180 3.6 1.5
310-helix -49 -26 180 3.0 2.0
-helix -57 -70 180 4.4 1.15
Polyproline I -83 +158 0 3.33 1.9
Polyproline II -78 +149 180 3.0 3.12
Polyproline III -80 +150 180 3.0 3.1
A diagram showing the dihedral bond angles for regular polypeptide conformations.Note: omega = 0º is a cis peptide bond and omega = 180º is a trans peptide bond.
Schemes for antiparallel (a) and parallel (b) -sheets
• 1/3 peptide-bond dipole is parallel to strand direction for parallel -sheets
•1/15 peptide-bond dipole is parallel to strand direction for antiparallel -sheets
Dipole moment of -sheets
The -sheets are stabilized by long-range hydrogen bonds and side chain contacts
-sheets are pleated
• Backbone hydrogen bonds in -sheets are by about 0.1 Å shorter from those in -helices and more linear (160o) than the helical structures (157o)
• -sheets are not initiated by any specific residue types
•Pro residues are rare inside -strands; one exception is dendrotoxin K (1DTK)
And the ruffles add flavor!
-sheet chiralityBecause of interactions between the side chains of the neighboring strands, the -strands have left-handed chirality which results in the right twist of the -sheets
N-end
C-end
The degree of twist is determined by the tendency to save the intrachain hydrogen bonds in the presence of side-chain crowding
anti-parallel
parallel
‘twisted’
The geometry of twisted -sheets
The geometry of parallel twisted sheets
thioredoxin
trioseposphate isomerase
Parallel -structures occur mostly in proteins where the -sheet is covered by -helical helices
Geometry of antiparallel sheets (mostly outside proteins and between domains)
twisted (coiled) Multistrand twisted
Cyllinders
Threestrand with a -bulge
Three strand helicoidal
Cupola (dome)
Example of a coiled two-strand antiparallel -sheet
TERMOLIZYNA-RASMOL
Stereoscopic views of some examples of two-strand, coiled antiparallel -structures: a) pancreatic trypsin inhibitor, b) lactate dehydrogenase, c) thermolysin.
Example of a three-strand antiparallel -structure
•The central strand is least deformed
Ribonuclease A
A fragment of the antiparallel -cyllinder in chymotrypsin, with local deviations from the ideal -structure. Note that the divergence of the strands near cyllinder edge which occurrs to relieve local strains results in twisting the strands.
The geometry of twisted) structures
In cyllindrical antiparallel -sheets (as in parallel -sheets ) strand conformation at cyllinder ends is often irregular.
The interstrand angle depends on the number of strands in a cyllinder.
Example of a cyllindrical (-barrel) structure
Large antiparallel -sheets: twisted planes not barrels
2CNA (3CNA) and 3BCL
Concavalin
-bulges
Local -state at the bulging residue
X
2
1
Four types of -bulges
Classical
, angles of residue 1 as for structures; those for residue 2 and X for -structures
G1
Link of a - and turn structure
Gly almost exclusively at position 1
Broad
Larger H-bond distances between the consecutive strands
GX
Strong preference for Gly at position X
-sheet amphipacity
1B9C - RASMOL
The hydrophobic and hydrophilic side chains are arranged on alternative sides of a -sheet.
Length of -sheets in proteins20 Å (6 aa residues)/strand on average, corresponding to single domain length
Usually up to do 6 -strands (about 25 Å)
Usually and odd number of -strands because of better accommodation of hydrogen bonds in a -sheet
antiparallel
There are two basic categories of connections between the individual strands of a beta sheet (Richardson, 1981). When the backbone enters the same end of the sheet that it left it is called a hairpin connection and when the backbone enters the opposite end it is called a crossover connection.
Crossover connections can be thought of as a type of helical connection of the strand ends. In globular proteins, right-handed crossovers are the rule, although a few examples of left-handed crossovers are available (e.g., subtilisin and glucose phosphate isomerase).
parallel
Covalent interstrand connections in sheets
antiparallel
parallel
-sheet topology in proteins
-hairpin connects the C-end of one strand with the N-end of another strand. If the strands are neighbors in sequence, this connection is denoted as „+1”; if they are separated by one strand it is denoted as „+2”.
The cross-over connection denoted as +1x if the connected strands are neioghbors in sequence or +2x if they are second neighbors
Topologia struktur białkowych
Typical connections in structures
An example of complex beta-sheets:Silk Fibroin
- multiple pleated sheets provide toughness & rigidity to many structural proteins.
and connections
1CTF 100-120 - RASMOL
Conserved Gly residues and hydrophobic interactions between residues at positions Gly-4 and Gly+3
„Paperclips”• Turn structures at the ends of -helices
PCY 74-80 - RASMOL
Green key and -arch
Secondary Structure Preference• Amino acids form chains, the sequence or primary structure.
• These chains fold in -helices, -strands, -turns, and loops (or for short, helix, strand, turn and loop), the secondary structure.
• These secondary structure elements fold further to make tertiary structure.
• There are relations between the physico-chemical characteristics of the amino acids and their secondary structure preference. I.e., the - branched residues (Ile, Thr, Val) like to sit in -strands.
• We will now discuss the 20 ‘natural’ amino acids, and we will later return to the problem of secondary structure preferences.
Secondary Structure Preferences helix strand turn•Alanine 1.42 0.83 0.66 •Arginine 0.98 0.93 0.95•Aspartic Acid 1.01 0.54 1.46•Asparagine 0.67 0.89 1.56•Cysteine 0.70 1.19 1.19•Glutamic Acid 1.39 1.17 0.74 •Glutamine 1.11 1.10 0.98•Glycine 0.57 0.75 1.56•Histidine 1.00 0.87 0.95•Isoleucine 1.08 1.60 0.47•Leucine 1.41 1.30 0.59•Lysine 1.14 0.74 1.01•Methionine 1.45 1.05 0.60•Phenylalanine 1.13 1.38 0.60•Proline 0.57 0.55 1.52•Serine 0.77 0.75 1.43•Threonine 0.83 1.19 0.96•Tryptophan 1.08 1.37 0.96•Tyrosine 0.69 1.47 1.14•Valine 1.06 1.70 0.50
Secondary Structure Preferences• helix strand turn• Alanine 1.42 0.83 0.66 • Glutamic Acid 1.39 1.17 0.74 • Glutamine 1.11 1.10 0.98• Leucine 1.41 1.30 0.59• Lysine 1.14 0.74 1.01• Methionine 1.45 1.05 0.60• Phenylalanine 1.13 1.38 0.60
• Subset of helix-lovers. If we forget alanine (I don’t understand that things affair with the helix at all), they share the presence of a (hydrophobic) C-, C- and C- (S- in Met). These hydrophobic atoms pack on top of each other in the helix. That creates a hydrophobic effect.
Secondary Structure Preferences• helix strand turn• Isoleucine 1.08 1.60 0.47• Leucine 1.41 1.30 0.59• Phenylalanine 1.13 1.38 0.60• Threonine 0.83 1.19 0.96• Tryptophan 1.08 1.37 0.96• Tyrosine 0.69 1.47 1.14• Valine 1.06 1.70 0.50
• Subset of strand-lovers. These residues either have in common their -branched nature (Ile, Thr, Val) or their large and hydrophobic character (rest).
Secondary Structure Preferences
helix strand turn• Aspartic Acid 1.01 0.54 1.46• Asparagine 0.67 0.89 1.56• Glycine 0.57 0.75 1.56• Proline 0.57 0.55 1.52• Serine 0.77 0.75 1.43
• Subset of turn-lovers. Glycine is special because it is so flexible, so it can easily make the sharp turns and bends needed in a -turn. Proline is special because it is so rigid; you could say that it is pre-bend for the -turn.
• Aspartic acid, asparagine, and serine have in common that they have short side chains that can form hydrogen bonds with the own backbone. These hydrogen bonds compensate the energy loss caused by bending the chain into a -turn.