Topology diagrams are useful for classification of protein

structures

Topology diagrams represents the connectivity and the strand
order
Secondary structures are represented by 3 different symbols
Cylinders for alpha helix, arrows for beta strands and ribbons
for remaining part such as loops and turns
Topology diagrams for beta sheets includes
The no of strands
Relative directions
Strand order (how the strands are connected along the
polypeptide
Secondary structure elements are connected to form
simple motifs

Simple combinations of a few secondary structure
elements with a specific geometric arrangement
They may have functional and structural significance
Since motifs contain more than one secondary structural
element, these are referred to as super secondary
structures
Supersecondary structures as combinations of alpha-
helices and beta-structures connected through loops that
form patterns that are present in many different protein
structures.
Simple motifs can combine to form more complex motifs
Common Motifs

Helix turn helix
Beta hairpin
Beta barrel, Greek key
Beta alpha beta

The simplest motif with a specific function consists of two helices,
connected by a short loop or a turn.
lambda Cro
Specific for DNA Binding proteins
The calcium-binding motif EF hand
(Parvalbumin, calmodulin, troponin C and other calcium binding
proteins)
The calcium-binding motif, EF-hand
The calcium-binding motif EF hand

The motif provides a scaffold that holds the calcium ligands in the proper position to
bind and release calcium.

The motif comprises two helices, E and F, that flank a loop of 12 contiguous residues.
Five of the loop residues are calcium ligands, and their side chains should contain an
oxygen atom and preferably be Asp or Glu. Residue 6 of the loop must be a glycine
because the side chain of any other residue would disturb the structure of the motif.
Finally, a number of side chains form a hydrophobic core between the a helices and thus
must be hydrophobic.
The calcium-binding motif, EF-hand
The calcium atom is bound to one of the motifs in the muscle protein
troponin C through six oxygen atoms: one each from the side chains of
Asp(D)9, Asn(N)11, and Asp(D)13; one from the main chain residue 15,
and two from the side chain of Glu(E) 20. In addition a water molecule
is bound to the calcium atom
Hairpin beta motif: two antiparallel beta strands
connected by a loop

2 antiparallel beta-strands + beta-turn = hairpin
The simplest motif involving strands two adjacent anti-
parallel strands joined by a loop
This motif is called either a hairpin or a - unit and occurs
quite frequently
The lengths of the loop regions are generally from two to five
residues
There is no specific function associated with this motif.
The hairpin -motif occurs frequently in protein structures
The Greek key motif is found in antiparallel -sheets - four
adjacent antiparallel beta strands folded upon itself
Long insertion between
strands 3 and 4
Greek Ornamental fret
Suggested folding pathway from a hairpin-like structure to the
Greek key motif. Beta strands 2 and 3 fold over such that strand
2 is aligned adjacent and antiparallel to strand 1.
The -- motif contains two parallel -strands

If two adjacent strands are consecutive in the amino acid
sequence, the two ends that must be joined to form parallel
strands of a sheet are at opposite edges of the sheet
The connection between the two ends are frequently made by
helices
The motif that is formed is thus a strand followed by a loop,
an helix, another loop, and, finally, the second strand
The loop connecting the carboxy end of the strand with the
amino end of the helix often have conserved amino acid
sequences in homologous proteins and are involved in forming
the active site of these structures.
Two adjacent parallel beta strands are usually connected by an
alpha helix from the C terminus of strand 1 to the N terminus
of strand 2
Most protein structures that contain parallel beta sheets are
built up from combinations of such -- motifs
Eg., Triosephosphate isomerase
Handedness of the -- motif

The motif can in principle occur in two different "enantiomeric forms",
with the helix either above or below the plane of the sheet.
Essentially every -- motif in the known protein structures has been
found to be right-handed (a). No convincing explanation has been found
for this regularity. This handedness has important structural and
functional consequences when several of these motifs are linked into a
domain structure.
Large polypeptide chains fold into several domains

A domain is defined as a polypeptide chain or a part of a
polypeptide chain that can fold independently into a stable
tertiary structure
A domain is considered the fundamental unit of protein
structure, folding, function, evolution and design.
Often, the different domains of a protein are associated with
different functions
Proteins may comprise a single domain or as many as several
dozen domains
There is no fundamental structural distinction between a
domain and a subunit
A protein is a combination of domains
Protein1

Protein2

Protein3

Domain Functions

Often each domain has a separate function to perform for
the protein, such as:
Bind a small ligand
Spanning the plasma membrane (transmembrane proteins)
Contain the catalytic site (enzymes)
DNA-binding (in transcription factors)
Providing a surface to bind specifically to another protein

Domains are built from structural motifs

Domains are formed by different combinations of
secondary structure elements and motifs
Sequentially adjacent motifs, are usually close together in
the three-dimensional structure
A polypeptide chain is thus a sequential arrangement
motifs. Some combinations seem to be structurally
favored
Similar domain structures frequently occur in different
proteins with different functions and with completely
different amino acid sequences.
Simple motifs combine to form complex motifs