A detailed explanation of TOPS cartoons
Anyone who has viewed the full atomic representation of a protein structure, either on a computer screen or on paper, will agree that such diagrams can be complicated and difficult to interpret. There are a number of simplified representations which make interpretation easier. For instance, many programs for display of protein structures produce formats in which only the protein backbone is displayed, and even simpler formats where secondary structures are represented by arrows and cylinders (eg. MOLSCRIPT and RIBBONS).
Even more simplified representations of protein folds are the so-called protein topology cartoons. These diagrams are two-dimensional schematic representations of protein structures. They represent the structure as a sequence of secondary structure elements (helices and strands), and illustrate the relative spatial position and direction of these elements. A variety of topology cartoons have been used over the years, and while these differ in details, they share the same philosophy of a simplified representation of the protein structure that helps understanding of the overall fold, and makes visual comparison of different folds easier.
The cartoons represented on this web site take a form closely related to the that of the cartoons described by Sternberg and Thornton and produced automatically by the program TOPS of Flores and co-workers. The cartoons are perhaps best explained by a few examples. The first example we will consider is the the super-oxide dismutase structure shown in figure 1 below.
In this figure, the three-dimensional ribbon diagram of the protein is shown on the left and the TOPS cartoon on the right. The ribbon diagram shows beta strands as yellow arrows and alpha or 3
Now lets look at the TOPS cartoon. First, the peptide chain runs from N terminus N1 to C terminus C2 and can be traced by following the connecting lines from symbol to symbol. The triangular symbols represent beta strands and the circular one helices. The symbols should be thought of as representing secondary structure elements which are perpendicular to the plane of the diagram. They have a direction ( N to C ) which is either “up” ( out of the plane of the diagram ) or down ( into the plane of the diagram ). “Up” strands are represented by upward pointing triangles and “Down” ones by downward pointing triangles. The five stranded sheet is represented by the upper horizontal row of five triangles and the four stranded sheet by the lower one. The alternation of strand directions along these rows shows that the sheets are anti-parallel. The observant reader may have noticed that the connecting lines between the triangular strand symbols are drawn sometimes to the edge of the symbol and sometimes to the centre. This is in fact another way of showing the direction of the secondary structure element: if the amino (N) terminal connection is drawn to the edge of the symbol and the carboxy (C) terminal connection to the centre, then the direction is up; otherwise the N terminal connection is drawn to the centre and the C terminal one to the edge, and the direction is down. So there are two ways in which the direction of strands is shown, but the direction of helices must be deduced by looking at the connecting lines.
The TOPS cartoon is two-dimensional, and hence ideal for display on paper or any other two dimensional medium. It also easier for the human brain to comprehend, requiring less three-dimensional imagination than the ribbon diagram. However, the cartoon implies a three-dimensional structure through the assignment of a direction to the strands perpendicular to the plane of the diagram. It is in this implied third dimension that much interesting topological information about the protein structure is held. In figure 1 the two sheets pack into a sandwich structure and this is illustrated in the cartoon by the fact that they are drawn in adjacent horizontal layers one below the other. This sandwich structure, and the Greek key super-secondary structure elements within it, has a well defined chirality, and this chirality is implied in the TOPS cartoon through the existence of the implied third dimension.
Now lets look at another example with more helices. Consider the four layer sandwich structure of the protein shown in figure 2 below.
Again we’ve chosen a protein whose core is a beta sandwich structure. Generally TOPS cartoons are more useful for structures with substantial beta secondary structure content. This is because beta strands associate into larger super structures such as sheets and barrels through well defined hydrogen bond relationships, which imply well defined relative directions for the strands. This type of association is absent for helices, relative directions have to be calculated using geometric considerations, and often in all alpha folds helical packing angles differ substantially from the parallel or anti-parallel dichotomy implied by TOPS cartoons ( a counter example to this generalization is the up/down four helix bundle fold ).
So back to the example of figure 2. Again we have the beta sandwich, though this time the sheets are mixed rather than pure anti-parallel. The helices are positioned with respect to the sandwich to give them a position which approximately corresponds to their position in the three-dimensional structure and a direction which is calculated geometrically. Note that beta-alpha-beta units, such as the one highlighted in green in the diagram are drawn with the same chirality as they have in the three-dimensional structure. This correct chirality is also enforced for beta – X – beta structures where the two strands are parallel and part of the same sheet and X is up to four other secondary structure elements.
We have now looked at two example tops diagrams in some detail and you should have a good understanding of what they mean which will equip you to understand most tops diagrams. There are a couple more things of which you should be aware. The examples above dealt with beta sheets and sandwiches and also alpha helices; as yet we haven’t discussed beta barrels. For our purposes a beta barrel is a beta sheet which is curved round so that the “left” and “right” edge strands are able to hydrogen bond together to create a cyclic arrangement of hydrogen bonds. Tops diagrams of these structures show the strands plotted on the circumference of a circle, as shown in figure 3 which is a tops diagram for a porin structure containing a 16 strand anti-parallel barrel.
There is one more type of beta structure found in TOPS cartoons. Above we gave the impression that beta sheets are always plotted as a horizontal row of triangular symbols. This is not actually the case: occasionally a structure will contain a beta sheet with a very high degree of curvature for which a linear plot would be confusing. In this case the sheet is plotted as triangles lying on a circular arc, as shown in the example of figure 4, which is a tops diagram for a lipid binding protein.
In this diagram the triangles lie on a circular arc but there is a space between the edge strands of the sheet indicating the lack of the necessary hydrogen bonds required to form a beta barrel.
Finally, we should mention proteins with more than one structural domain. TOPS cartoons for these proteins show the domains separately. In the most general case the peptide chain can be considered to be divided into segments each of which appears in only one structural domain. A TOPS diagram for such a protein is shown below in figure 5.
This protein has two structural domains, the first shown in figure 5a, the second in figure 5b. The peptide chain is divided into four segments and these are shown in the figure as N1->C2, N2->C3, N3->C4 and N4->C5. Tracing through the chain from N to C terminus we see that the first segment (N1->C2) lies in the first domain. The chain then crosses to the second domain, and the second segment (N2->C3) lies in this domain. The third segment (N3->C4) lies back in the first domain and the final segment is back in the second domain.
In the general case the peptide chain is divided into a number of segments N
You should now understand any tops diagram.
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