1. Motifs and Domains
Presented By: Maliha Rashid
M.Phil Biotechnology
UIBB, PMAS Arid Agriculture University Rawalpindi, Pakistan
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2. Motifs
• small regions of protein three-dimensional structure or amino acid sequence
shared among different proteins.
• Signatures of protein families and can often be used as tools for the prediction of
protein function.
• They are recognizable regions of protein structure that may (or may not) be
defined by a unique chemical or biological function.
• can’t exist independently
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3. Motifs – Supersecondary Structures
• Supersecondary structure refers to a combination of secondary
structure elements, such as
beta-alpha-beta units
helix-turn-helix motif
• also referred to as structural motifs
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4. Function of motifs
• Describe short amino acid arrangements that are shared by protein
family members
• Designed to be used in conjugation with protein sequence
databases to assign putative functions to unknown proteins
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6. Alpha-loop-Alpha
• These are found in DNA-binding proteins that regulate transcription and
also in calcium-binding proteins, in which the motif is often called the EF
hand. The loop region in calcium-binding proteins is enriched in Asp, Glu,
Ser, and Thr.
Basic helix-turn-helix from the c-Myc protein (1NKP)
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7. Beta-hairpin or beta-turn
• This motif is present in most antiparallel beta structures, both as an
isolated ribbon and as part of beta sheets connected through a
loop
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8. 2D homology map of beta-hairpin
from bovine pancreatic trypsin
inhibitor (1k6u)
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9. Greek Key
The "Greek Key" symbol represents infinity and the eternal flow of
things and resembles in part primitive keys. The Greek Key motif in
proteins can be seen in the structure of antiparallel beta sheets in the
ordering of four adjacent antiparallel beta strands
Greek Key Motif
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10. Figure shows a partial 2D
topology map of
Staphylococcus nuclease
(2SNS)
Greek Key motif from
Staphylococcus nuclease
(2SNS)
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11. Beta-Alpha-Beta
The motif is a common way to connect two parallel beta strands as
compared to beta hairpins, which are used to connect antiparallel beta
strands.
Beta alpha beta motif from
triose phosphate isomerase
(1amk)
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12. Larger Structural Motifs - Protein Architecture
• The Rossman Fold
• The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel.
• Beta Helices
• Beta Propellors
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13. The Rossman Fold
Structural motifs can serve particular functions within proteins such as enabling the binding of substrates or
cofactors.
• For example, the Rossmann fold is responsible for binding to nucleotide cofactors such as nicotinamide
adenine dinucleotide (NAD+).
• composed of six parallel beta strands that form an extended beta sheet
• The first three strands are connected by α-helices resulting in a beta-alpha-beta-alpha-beta structure.
• Overall, the strands are arranged in the order of 321456 (1 = N-terminal, 6 = C-terminal).
• Five stranded Rossmann-like folds are arranged in the sequential order 32145.
The overall tertiary structure of the fold resembles a three-layered sandwich.
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14. Cartoon diagram of the Rossmann Fold
(helices A-F red and strands 1-6 yellow)
from E. coli malate dehydrogenase enzyme.
Schematic diagram of the six stranded Rossmann fold
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15. Continued….
• One of the features of the Rossmann fold is its co-factor binding specificity
• The most conserved segment of Rossmann folds is the first beta-alpha-beta
segment
• Since this segment is in contact with the ADP portion of dinucleotides such as
FAD, NAD and NADP it is also called as an "ADP-binding beta-beta fold"
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16. Databases and software to predict/find motifs
• Motifscan
• InterProScan
• PROSITE
• Pfam Scan (http://pfam-legacy.xfam.org/)
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21. What Are Domains?
• distinct functional and structural units in a protein
• region of a protein's polypeptide chain that is self-stabilizing and that folds independently
from the rest
• are regions of a protein that has a specific function
• a compact folded three-dimensional structure
• 50 amino acids to 250 amino acids in length
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22. Continued…
• Often has sequence or structural resemblance to other protein
structures or domains
• fundamental units of tertiary structure
• each domain containing an individual hydrophobic core built from
secondary structural units connected by loop regions
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23. Examples of domains
• Zinc fingers are an example of small protein domains – a common
DNA binding domain
• consists of ∼30 amino acids that may recognize three base pairs of
DNA
• can recognize and bind to a specific DNA into the genome
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24. Example:
pyruvate kinase
all-β nucleotide binding domain (in blue)
an α/β-substrate binding domain (in grey)
an α/β-regulatory domain (in olive green)
Each domain in this protein occurs in
diverse sets of protein families
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25. Types
1. α category domains consist almost entirely of α
helices and loops
2. Β category consist only β sheets and loops/ Ββ turns
3. α/ β category domains have super secondary such
structures such as the βαβ motif
4. α + β category domains consist of local clusters of a helices and
β sheet (where each type of structure
arises from separate contiguous regions
in the polypeptide chain
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26. Significance of Domains
• Domain are independently stable, DOMAINS can be ‘swapped’ by genetic
engineering between one proteins and another to make chimeric protein
• Metabolic Engineering can be placed by altering protein domain.
• Better analysis of protein, which will help in better understanding of the
different domain causing different function in protein.
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28. Domain Servers
The three major domain servers are used to make complete analyses
of the domain contained in sequence
1. InterProScan
2. CD-Search
3. Motif-Scan
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is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone
The Rossmann fold is one of the most commonly observed structural domains in proteins. The fold is composed of consecutive alternating β-strands and α-helices that form a layer of β-sheet with one (or two) layer(s) of α-helices.
