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SUPERSECONDARY
STRUCTURE, DOMAINS AND
TERTIARY STRUCTURE
Levels of protein structure organization
Between secondary and tertiary
structure
• Supersecondary structure: arrangement of
elements of same or different secondary
structure into motifs; a motif is usually not
stable by itself.
• Domains: A domain is an independent unit,
usually stable by itself; it can comprise the
whole protein or a part of the protein.
The Ramachandran map
Conformations of a terminally-blocked amino-acid residue
E
Zimmerman, Pottle, Nemethy, Scheraga,
Macromolecules, 10, 1-9 (1977)
C7eq
C7ax
Secondary Structure Preferences
•
•
•
•
•
•
•
•
•
Alanine
Glutamic Acid
Glutamine
Leucine
Lysine
Methionine
Phenylalanine
helix
1.42
1.39
1.11
1.41
1.14
1.45
1.13
strand
0.83
1.17
1.10
1.30
0.74
1.05
1.38
turn
0.66
0.74
0.98
0.59
1.01
0.60
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-b, Cg and C-d (S-d in Met). These hydrophobic atoms pack on top of each other in
the helix. That creates a hydrophobic effect.
Secondary Structure Preferences
•
•
•
•
•
•
•
•
Isoleucine
Leucine
Phenylalanine
Threonine
Tryptophan
Tyrosine
Valine
helix
1.08
1.41
1.13
0.83
1.08
0.69
1.06
strand
1.60
1.30
1.38
1.19
1.37
1.47
1.70
turn
0.47
0.59
0.60
0.96
0.96
1.14
0.50
• Subset of strand-lovers. These residues either have in common their bbranched nature (Ile, Thr, Val) or their large and hydrophobic
character (rest).
Secondary Structure Preferences
•
•
•
•
•
•
•
helix
Aspartic Acid 1.01
Asparagine
0.67
Glycine
0.57
Proline
0.57
Serine
0.77
strand
0.54
0.89
0.75
0.55
0.75
turn
1.46
1.56
1.56
1.52
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 b-turn. Proline is special
because it is so rigid; you could say that it is pre-bend for the b-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 b-turn.
Dominant b-turns
Idealized hydrogen-bonded helical structures:
310-helix (left), a-helix (middle), p-helix (right)
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.
f and y angles of regular and polyproline helices
Structure
F
Y
w
a-helix
-57
-47
180
+3.6
1.5
310-helix
-49
-26
180
+3.0
2.0
p-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
residues/turn
turns/residue
Length of a-helices in proteins
10-17 amino acids on average (3-5 turns); however much longer helices occur in
muscle proteins (myosin, actin)
Antiparallel sheet (L6-7)
The side chains have alternating arrangement; usually hydrophobic on one and hydrophilic on the opposite site
resulting in a bilayer
2TRX.PDB
Parallel sheet (L6-7)
The amino acid R groups face up & down from a beta sheet
2TRX.PDB
Structure
F
Antiparallel b
Y
w
Residues/turn
Distance along axis/turn
-139 +135 -178
2.0
3.4
Parallel b
-119 +113 180
2.0
3.2
a-helix
-57
-47
180
3.6
1.5
310-helix
-49
-26
180
3.0
2.0
p-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) b-sheets
b-sheets are pleated
b-sheet chirality
Because of interactions between the side chains of the neighboring strands, the b-strands
have left-handed chirality which results in the right twist of the b-sheets
N-end
C-end
Length of b-sheets in proteins
20 Å (6 aa residues)/strand on average, corresponding to single
domain length
Usually up to do 6 b-strands (about 25 Å)
Usually and odd number of b-strands because of better
accommodation of hydrogen bonds in a b-sheet
Structural motifs (supersecondary structure)
b-hairpin I
b-hairpin II
b-corner)
helix hairpin
a-a corner
E-F hand
helix-turn-helix (HTH) motif
three-helix bundle
four-helix bundle
helix-b-hairpin (zinc finger
motif)
• bab motif
• babab motif (Rossman fold
•
•
•
•
•
•
•
•
•
•
• b-meander
• greek key motif
• Swiss, jellyroll or b-sandwich
motif
• horseshoe motif
• b-propellor
• b-helix
Example of a b-hairpin in bovine pancreatic
trypsin inhibitor– BPTI.
Example of a protein with two b-hairpins:
erabutoxin from whale.
Example of a b-meander: aspectrin SH3 domain (1BK2)
Example of a b-hairpin: tryptophan zipper (1LE0)
Helix Hairpin
Alpha alpha corner (L7.24)
E-F Hand motif
Helix E
helix F
Troponin C with four EF
motifs that bind calcium ions.
Because of high content of acidic amino-acid residues with side chains
pointing inside the loop, the EF-hand motif constitutes a calciumbinding scaffold in troponin, calmodulin, etc.
The Helix-Turn-Helix motif
• This motif is characteristic of proteins binding to the major DNA grove.
• The proteins containing this motif recongize palindromic DNA sequences.
• The second helix is responsible for nucleotide sequence recognition.
The Helix-Turn-Helix motif
Three-helix bundle (1BDD)
Four-helix bundle (3M9H)
The a-helix-b-hairpin motif (zinc finger)
b-a-b Motif (very important and very frequent)
Hydrophobic core between a-helix
and b-sheet
a/b horseshoe
The Greek Key Motif
The Greek-key motif as seen in proteins
Example of a protein with two
Greek key motifs: crystallin C.
Four Greek key motifs arranged into
two b-barrels.
RASMOL - gcrysb.pdb
The jellyroll topology
Example of a protein with jellyroll topology: Carbohydrate-Binding Module
Family 28 from Clostridium josui Cel5A (3ACI)
Example of a b-barrel (red fluorescent
protein; 3NED)
The b-helix
Example of a b-propellor motif : Thermostable PQQ-dependent
Soluble Aldose Sugar Dehydrogenase (3DAS)
Classification of three-dimensional structures of protein
Richardson’s classification
a – a-helices are only or dominant secondary-structure elements
(e.g., ferritin, myoglobin)
b – b-sheets are only or dominant elements (e.g., lipocain)
a/b – contain strongly interacting helices and sheets
a+b structures – contain weakly interacting or separated helices and
sheets
SCOP classification
Structural Classification Of Proteins
This is a hierarchical classification scheme with the following 4
levels:
1. Families – one family is comprised by proteins related
structurally, evolutionally, and functionally.
2. Superfamoilies – A superfamily is comprised by families of
substantially related by structure and function.
3. Folds – Superfamilies with common topology of the main portion
of the chain.
4. Classes - Groups of folds characterized by secondary structure: a
(mainly a-helices), b (mainly b-sheets), a/b (a-helices and bsheets strongly interacting), a+b (a-helices and b-weakly
interacting or not interacting), multidomain proteins (nonhomologous proteins with vert diverse folds).
[ http://scop.mrc-lmb.cam.ac.uk/scop/ ]
CATH classification (Class (C), Architecture(A), Topology(T), Homologous
superfamily (H))
Four hierarchy levels:
1.
Class (Level C): according to the content of secondary structure type a, b,
a&b (a/b and a+b), weakly or undefined secondary structure.
2.
Architecture. (Level A) – Orientation and connection topology between
secondary structure elements.
3.
Topology. (Level T) – based on fold type.
4.
Homoloous superfamilies. (Level H) – high homology indicating a common
anscestor:
-
>30% sequence identity OR
-
> 20% sequence identiy and 60% structural homology OR
-
> 60% structural homology and similar domains have similar function.
• Class(C)
derived from secondary structure
content is assigned automatically
• Architecture(A)
describes the gross orientation of
secondary structures, independent
of connectivity.
• Topology(T)
clusters structures according to
their topological connections and
numbers of secondary structures
• Homologous superfamily (H)
[ http://www.biochem.ucl.ac.uk/bsm/cath_new/ ]
Protein periodic table
W. Taylor and M. Hill
Layers
b-sheets: rectangles and circles; a—helics: filled circles