1. Motives of secondary structures
Consecutive elements of secondary structure can assemble together and form recurring or frequently found structures in protein folds (tertiary structure).
These special assemblies are called motives and represent supra-secondary elements, often associated with special structural or functional properties.
In a motif, a helices and/or b strands are linked together by loops of variable lengths; the main chain of the latter is devoid of regular structure.
The atom density in an assembled motif is generally higher than that before the assembly.
ca-Prot_Enz

2. The helix-turn-helix motif
Two a helices that are connected by a short loop region in a specific geometric arrangement. Two such motifs are shown: (a) the DNA-binding motif and (b) the calcium-binding motif which is present in many proteins whose function is regulated by calcium
ca-Prot_Enz

3. The DNA binding motif a c b d
Cro molecules from bacteriophage lambda form dimers both in solution and in the crystal structure.
The DNA-binding helix-turn-helix motif in lambda Cro.
The helix-turn-helix motif sitting in the major groove of DNA.
A schematic space-filling model of the dimer of Cro bound to a bent B-DNA molecule.
ca-Prot_Enz

4. EcoRV binding and restriction
5’-XXXGAT ATCXXX-3’
3’-XXXCTA TAGXXX-5’
Schematic representation of the proposed DNA-sequence recognition mechanism by EcoRV in which only the most important differences between the states are shown. First, EcoRV in an open state binds to a random DNA sequence and forms a loosely bound open complex (step 1). Then, upon recognition of the outer base pairs, GAxxTC, a partially bound closed complex with bent DNA is formed (step 2). Finally, recognition of the center base pairs, xx = TA, results in a tightly bound cleavage-ready complex, with a full kink of 50° (step 3). The distance between the “arms” of the protein, E, decreases from step 1 to step3 (E0 < E1 < E2 < E 3). Simultaneously, the distance between the protein and the DNA, D, becomes smaller (D0 < D1 < D2 < D3). From Zahran et al, JMB 2010.
ca-Prot_Enz

5. The Ca-binding motif
(a) The calcium-binding motif is symbolized by a right hand. Helix E (red) runs from the tip to the base of the forefinger. The flexed middle finger corresponds to the green loop region of 12 residues that binds calcium (pink). Helix F (blue) runs to the end of the thumb. (b) The calcium atom is bound to one of the motifs in the muscle protein troponin-C through six oxygen atoms: 5 from the side chains of Asp and Glu; and one from the main chain. In addition, a water molecule (W) is bound to the calcium atom. (c) Schematic diagram illustrating that the structure of troponin-C is built up from four EF motifs---colored as in (a). Two of these bind Ca.
ca-Prot_Enz

6. Antiparallel beta hair pin
Adjacent antiparallel b strands are joined by hairpin loops. Such loops are frequently short and do not have regular secondary structure. Nevertheless, many loop regions in different proteins have similar structures. (a) Histogram showing the frequency of hairpin loops of different lengths in 62 different proteins. (b) The two most frequently occurring two-residue hairpin loops; Type I turn to the left and Type II turn to the right. Bonds within the hairpin loop are green. [(a) Adapted from B.L. Sibanda and J.M. Thornton, Nature 316: , 1985.]
ca-Prot_Enz

7. The beta hair-pin
The hairpin motif is very frequent in b sheets and is built up
from two adjacent antiparallel b strands that are joined by a loop region.
Two examples of such motifs are shown. (a) Schematic diagram of the structure of bovine trypsin inhibitor. The hairpin motif is colored red. (b) Schematic diagram of the structure of the snake venom erabutoxin. The two hairpin motifs within the b sheet are colored red and green. (Adapted from J. Richardson.)
ca-Prot_Enz

8. Possible arrangements of two consecutive b hair pins
Two sequentially adjacent hairpin motifs can be arranged in 24 different ways into a b sheet of four strands. (a) Topology diagrams for those arrangements that were found in a survey of all known structures in The Greek key motifs in (i) and (v) occurred 74 times, whereas the arrangement shown in (viii) occurred only once. (b) Topology diagrams for those 16 arrangements that did not occur in any structure known at that time. Most of these arrangements contain a pair of adjacent parallel b strands.
ca-Prot_Enz

9. The Greek key
The Greek key motif is found in antiparallel b sheets when four adjacent b strands are arranged in the pattern shown as a topology diagram.
The motif occurs in many b sheets and is exemplified here by the enzyme Staphylococcus nuclease. The four b strands that form this motif are colored red and blue.
Suggested folding pathway from a hairpin like structure to the Greek key motif.
ca-Prot_Enz

10. The b-a-b motif
Two adjacent parallel b strands are usually connected by an a helix from the C-terminus of strand 1 to the N-terminus of strand 2.
Most protein structures that contain parallel b sheets are built up from combinations of such b-a-b motifs (right-handed structures).
ca-Prot_Enz

11. From motifs to domains
Motifs that are adjacent in the amino acid sequence are also usually adjacent in the three-dimensional structure.
Triose-phosphate isomerase is built up from four b-a-b-a motifs that are consecutive both in the amino acid sequence (a) and in the three-dimensional structure (b).
ca-Prot_Enz

12. The Felix fold
Four-helix bundles often occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the 3-D structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core. (a) Representation of the path of the polypeptide chain in a four-helix-bundle domain. Red cylinders are a helices. (b) View of a projection down the bundle axis. Large circles represent the main chain of the a helices; small circles are side chains. Green circles are the buried hydrophobic side chains; red circles are mainly hydrophilic side chains exposed on the surface of the bundle.
ca-Prot_Enz

13. Felix structures
The polypeptide chains of cytochrome b562 and human growth hormone both form four-helix-bundle structures.
In cytochrome b562 (a) adjacent helices are antiparallel, whereas the human growth hormone (b) has two pairs of parallel a helices joined in an antiparallel fashion.
ca-Prot_Enz

14. Felix structures
Schematic diagram of the dimeric Rop molecule. Each subunit comprises two a helices arranged in a coiled-coil structure with side chains packed into the hydrophobic core according to the "knobs in holes" model. The two subunits are arranged in such a way that a bundle of four a helices is formed.
Schematic diagram of the structure of one domain of a bacterial muramidase. The structure is built up from 27 a helices (450 aa) arranged in a two-layered ring. The ring has a large central hole, like a doughnut, with a diameter of about 30 angstrom.
ca-Prot_Enz

15. The globin fold
Schematic diagram of the globin domain. The eight alpha helices are labeled A-H. A-D are red, E and F green, and G and H blue. The heme group is shown in white. (Adapted from originals provided by A. Lesk.)
ca-Prot_Enz

16. Ridges and grooves – topography of a helices
The side chains on the surface of an a helix form ridges separated by grooves. (a) An a helix with each residue represented by the first atom in the side chain, Cb. (b) The surface relief of a polyalanine a helix in the orientation shown in (a). Sections are cut through a space-filling model and superimposed. The residue numbers are placed on the side-chain atom. The ridges caused by the side chains separated by four residues are shown as lines. (c) The same as (b), but here the ridges are caused by side chains separated by three residues
ca-Prot_Enz

17. The topography of packing
Fitting the ridges from one helix into the grooves of the other helix results in tight packing. (a) Two a helices, I and II, with ridges from side chains separated by four residues. Panels 1 and 2 are the same view of the two a helices. In panel 3 the blue helix is turned over through 180o to form an interface with the red helix. In panel 4 the orientation of the helices has been rotated 50o to pack the ridges of one helix into the grooves of the other.
(b) In the red helix the ridges are formed by side chains separated by four residues and in the blue a helix by three residues. The helices are rotated 20o in order to pack ridges into grooves, in a direction opposite that in (a). (Adapted from C. Chothia et al., Proc. Natl. Acad. Sci. USA 74: , 1977).
ca-Prot_Enz

18. Hemoglobin: a heterotetramer
The hemoglobin molecule is built up of four polypeptide chains: two a chains and two b chains.
Each chain has a three-dimensional structure similar to that of myoglobin: the globin fold. In sickle-cell hemoglobin Glu 6 in the b chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of
hemoglobin was determined in 1968 to 2.8 A resolution in the lab of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.
ca-Prot_Enz

19. Fibroid polymerization in sickle-cell hemoglobin
Electron micrographs of sickle-cell hemoglobin fibers are shown in cross-section in (b) and along the fibers in (c). [(b) and (c) from J.T. Finch et al., Proc. Natl. Acad. Sci. USA 70: , 1973.]
Sickle-cell hemoglobin molecules polymerize due to the hydrophobic patch introduced by the mutation Glu 6 to Val in the b chain. The diagram (a) illustrates how this hydrophobic patch (green) interacts with a hydrophobic pocket (red) in a second hemoglobin molecule, whose hydrophobic patch interacts with the pocket in a third molecule, and so on (inset).
ca-Prot_Enz

20. The a helix coiled-coil structure
Schematic diagram of the coiled-coil structure. Two a helices are intertwined and gradually coil around each other.
Repetitive pattern of amino acids in a coiled-coil a helix.
(a) The amino acid sequence of the transcription factor GCN4 showing a heptad repeat of leucine residues. Within each heptad the amino acids are labeled a-g.
(b) Schematic diagram of one heptad repeat in a coiled-coil structure showing the backbone of the polypeptide chain. The a helices in the coiled-coil are slightly distorted so that the helical repeat is 3.5 residues rather than 3.6, as in a regular helix. There is therefore an integral repeat of seven residues along the helix.
ca-Prot_Enz

21. Stabilizing interactions in coiled-coil fold
Packing of hydrophobic side chains between the two a helices in a coiled-coil structure. Every 7th residue in both helices is a leucine, labeled "d." Due to the heptad repeat, the d-residues pack against each other along the coiled-coil. Residues labeled "a" are also usually hydrophobic and participate in forming the hydrophobic core along the coiled-coil.
Salt bridges can stabilize coiled-coil structures in heterodimeric coiled-coil structures. The residues labeled "e" and "g" in the heptad sequence are close to the hydrophobic core and can form salt bridges between the two a helices of a coiled-coil structure, the e-residue in one helix with the g-residue in the second and vice versa. (a) Schematic view from the top of a heptad repeat. (b) Schematic view from the side of a coiled-coil structure.
ca-Prot_Enz

22. Knobs in holes packing
Packing side chains in the hydrophobic core of coiled-coil structures according to the "knobs in holes" model. The positions of the side chains along the surface of the cylindrical a helix is projected onto a plane parallel with the helical axis for both a helices of the coiled-coil. (a), (b) Projected positions of side chains in helices 1 and 2.
(c) Superposition of (a) and (b) using the relative orientation of the helices in the coiled-coil structure. The side-chain positions of the first helix, the "knobs," superimpose between the side-chain positions in the second helix, the "holes." The green shading outlines a d-residue (leucine) from helix 1 surrounded by four side chains from helix 2, and the brown shading outlines an a-residue (usually hydrophobic) from helix 1 surrounded by four side chains from helix 2.
ca-Prot_Enz