BI-202 – Bioinformatics

Lecture 4 Super secondary structure, Structural Biology

Tertiary Structure & Fold Types
 Super secondary Structure
(Motifs)
Super secondary motifs are the
structures that are formed by the
combination of secondary
structures containing alpha-
helices and beta-pleated sheets.
These structures are found in
the globular proteins and are
joined by loop, turn, or
hairpin they are found in
globular proteins where
the bend is required.
 Classification of Super secondary structures
ALPHA HELIX
The structures are formed when alpha helixes are connected via a loop, turn, or
hairpin.
Helix turn helix
•Helix-turn-helix is a motif that could also be called an α-α type.
•It is composed of two anti-parallel α helices which are connected by a turn.
•It is a functional motif that is found in proteins that bind to DNA major and
minor grooves, along with in calcium binding proteins.
Function:
•Its major function is in DNA recognition, as one helix is involved in the
recognition and is known as “recognization helix” while another one stabilizes
the interaction between DNA and Protein.
•Also involved in the establishment of the structure of DNA.
•Promotes cell proliferation.
•Maintenance of the biological clock, circadian rhythms.
•It can initiate the transcription of DNA itself.
•It can regulate bacterial operons like lac operon, trp operon, etc.
Helix-loop-helix
•It is involved in the characterization of transcription
factors.
•One of the 2 helices is small and involved in the
dimerization by packing and folding against another helix.
•The larger one contains a DNA binding region.
Function
•This type of motif typically binds to a consensus sequence
called E-box (CACGTG).
•Helix loop helix motifs are dimeric each with one helix
containing a basic amino acid that facilitates the DNA
binding.
Helix-hairpin-Helix
•This type of motif is similar but also distinct in many ways from
helix-loop-helix and helix-turn-helix.
•These types of motifs are involved in non-sequence specific DNA
binding that occurs via the formation of hydrogen bonds between
the protein backbone nitrogen and phosphate groups.
For example
•5’-exonuclease domains of prokaryotic DNA polymerases.
•Viral exonucleases.
A-A corner:
•These motifs are short loops regions that connect the helices.
•The helices are perpendicular to each other.
Function
•This type of motif is also involved in DNA binding.
β Sheets
This type of motif contains beta-sheets which are connected
via hairpins hydrogen bonds.
•Beta hairpins are the post simplest super secondary
structure.
•They are abundantly presenting the globular proteins.
•They are also known as β-β unit or β-ribbon.
•Beta sheets are arranged in reverse sheets and look like a
hairpin.
•They occur in the short loop regions between antiparallel
hydrogen-bonded beta-sheets.
•2 antiparallel beta sheets and 1 beta-turn makes a beta-
hairpin.
Function
•No specific function is associated with it.
β-β corner
•It consists of 2 anti-parallel beta strands.
•It can change its direction at an angle of 90 degrees mean they are
perpendicular.
Greek key motif
•This motif formed by four sequentially connected beta strands
which are adjacent to each (geometrically aligned to each other).
•The strands are alternate to each other.
•The first strand of beta-sheet has (N- terminus) which connects
the last strand of beta-sheet having (C-terminus) and hydrogen
bond exists between them.
•Connecting loops between beta-sheets may be longer and they
may include secondary structures.
 Mix- super secondary structures

β-α-β motif
•These motifs contain 2 beta-sheets which are
connected by an alpha helix.
•Connection between this type of motif is from C
terminus to N terminus.
• Proteins containing beta-sheets are made up of these
types of motifs.
Function
The loops that connect both strands are involved in
ligand binding and motif is found in ion channels.
Rossmann fold
•It is a structural motif that is found in proteins that binds
to the nucleotides, co-factors such as FAD+, NAD+, and
NADP+.
•This motif consists of 2 alternate beta strands and alpha-
helical segments which are bound to each other via
hydrogen bonds.
•Occurs in nucleotide-binding proteins.
Function
It binds enzymes to nucleotides cofactor and also
contributes to substrate binding.
Zinc finger motif
•This motif is a small structural motif.
•It is coordinated by 1 or more than 1 zinc ion so that it can
stabilize the fold.
•Zinc ion is held in place by cysteine and 2 histidine R
groups.
Function
•This motif is found in proteins that interact with DNA,
RNA.
 Tertiary Structure of Proteins
The tertiary structure of a protein refers to its three-dimensional
shape, which is formed when the protein's secondary structure
elements (like α-helices and β-sheets) fold into a compact,
functional form. This level of structure is stabilized by various
interactions among the amino acid side chains, including:
•Hydrophobic interactions: Nonpolar side chains tend to cluster
together inside the protein, away from the aqueous environment.
•Hydrogen bonds: These form between polar side chains or
between polar side chains and the protein backbone.
•Ionic bonds (Salt bridges): Formed between positively and
negatively charged side chains.
•Disulfide bonds: Covalent bonds between the sulfur atoms of
cysteine residues, providing extra stability.
•Van der Waals interactions: Weak attractions between closely
positioned atoms.
 Fold Types in Tertiary Structure

The term fold refers to the overall shape or topology of a protein,

defined by how its secondary structure elements are arranged and
packed together. There are several common fold types, each
associated with specific structural patterns and often related to
particular functions.
Here are some of the major fold types:
1. α-Helical Folds
•All-α Fold: Comprised predominantly of α-helices.
•Examples:
• Four-helix bundle: Four α-helices packed together, often
seen in proteins involved in structural support or signal
transduction.
• Globin fold: A specific arrangement of α-helices found in
hemoglobin and myoglobin, involved in oxygen binding.
β-Sheet Folds
•All-β Fold: Comprised predominantly of β-sheets.
•Examples:
• Greek Key Fold: Four β-strands arranged in a
specific topology, common in immunoglobulins.
• β-Barrel: A cylindrical structure formed by β-
sheets, found in many membrane proteins and
transporters.
α/β Folds
•Mixed α/β Fold: Contains both α-helices and β-sheets,
often in alternating patterns.
•Examples:
• TIM Barrel (α/β Barrel): A common fold
where β-strands form a barrel surrounded by α-
helices, seen in many enzymes.
• Rossmann Fold: A fold with alternating β-
strands and α-helices, often involved in binding
nucleotides.
α+β Folds
•α+β Fold: Contains both α-helices and β-sheets, but arranged
separately within the protein structure.
•Examples:
• Ferredoxin Fold: Characterized by a mix of α-helices and
β-sheets, often involved in electron transfer.
• Lysozyme Fold: Contains separate α-helical and β-sheet
regions, functioning in breaking down bacterial cell walls.
β-Sandwich Folds
•Description: Two β-sheets packed against each other, forming a
sandwich-like structure.
•Examples:
• Immunoglobulin Fold: Found in antibody molecules,
consisting of a β-sandwich that provides structural stability
and binding specificity.
 Thank you
Dr. Vandana
School of Bioengineering and Food Technology Shoolini University
Village Bhajol, Solan (H.P)

8219057357 (Mob No.)

[email protected]