Protein and motif

1. Group Members
Fatima Khan (SP19-BSI-022)
Asma Saparas (SP19-BSI-007)
Nighat Rabbani (SP19-BSI-039)
Amna Ishtiaq (SP19-BSI-005)
PROTEIN MOTIFS, DOMAINS AND PPI

2. Motifs
• A motif is a short conserved sequence pattern.
• They are recognizable regions of protein structure.
• Super secondary structure
• Performs similar biological functions.
• They are not stable independently and are formed by the connected
alpha-helices and beta-sheets through loops.

3. Examples
• Zinc finger motif
• beta-hairpin motif
• Greek key motif
• Omega loop motif
• helix-loop-helix motif
• helix-turn-helix motif

4. Types of Motifs
1. Sequence motifs
• A protein sequence motif is an amino-acid
sequence pattern found in similar proteins;
change of a motif changes the corresponding
biological function.
2. Structure motifs
• It is a pattern in protein structure that is formed
by spatial arrangement of amino acids.
• Their role may be structural or functional.
• E.g., Beta turn

5. Significance
of Motif:
• A disease can easily be eliminated
permanently.
• Early detection of a disease.
• Better analysis of protein.
• Scientists will get a better tools to know more
about a disease, and can instruct experts and
doctors for better treatment and
understanding.

6. Motifs
Description:
1. Regular expressions
• Qualitative description of a motif eg. regular
expression C[AT]AAT[CG]X
2. Profiles
• Quantitative description of a motif eg.
position weight matrix
3. Profile HMMs
• Profile hidden Markov models (profile
HMMs) are statistical models of the primary
structure consensus of a sequence family.

7. Databases and
Tools
Motif Scan (includes Prosite, Pfam and
HAMAP profiles).
MOTIF Search
2ZIP (Server).
ScanProsite (Tool)
Scansite

8. Domains
• Protein domain is part of polypeptide chain that is
independently folded, to make stable tertiary structure
having a particular biological function.
• Proteins can have single or multiple domains, each having
particular function.
• One domain may appear in a variety of different proteins.

9. Functions
• Domain is fundamental structural and
functional unit of protein.
•
Serve as modules for building up large
assemblies such as virus particles or muscle
fibers
• Provide specific catalytic or binding sites as
found in enzymes or regulatory proteins.
•
Protein–protein interactions in processes of
cell adhesion, cell activation, and molecular
recognition
• Roles in the immune system.

10. Size
• In general, domains vary in length from between 25 amino acids up to
500 amino acids.
• Very short domains, less than 40 residues are often stabilized by
metal ions or disulfide bonds.
• Larger domains, greater than 300 residues, are likely to consist of
multiple hydrophobic cores

11. Examples
• Zinc Fingers
• EF Hand
• Src Homology 3(SH3)
Zing fingers
EF Hand

12. Types of Domains
• α -domains
found in myoglobin, where 8 alpha helices
found in 2 layers
• β-domains
include immunoglobulin and
Greek key motif
• β-barrel
• α- β barrel
TIM (triose phosphate isomerase)barrel
α -domains
α- β barrel
β-barrel
β-domains

13. Databases
● CATH
● SCOP
● InterPro-EMBL-EBL
● Pfam
● CDD (Conserved Domain Database)
● EXPASY -PROSITE :

14. EXPASY -PROSITE
We can retrieve the information that a particular protein
contain how many domains, which kind of domains and
the basic function of the domains present in our protein.

17. Difference:
MOTIFS Domains
A chain like biological structure
made up of connectivity between
secondary structural elements
An independent folding unit of 3D
protein structure
Not stable outside protein Stable outside protein
Secondary structure of protein Tertiary structure
Formed by connected alpha-helices
and beta-sheets through loops
Formed by formation of disulfide
bridges, ionic bonds and h-bonds
between amino acids side chains
Have structural function in protein Have functional importance
Have similar functions through
protein families
Have unique functions
Not independently stable Independently stable
Protein
2 domains
4 subunits
Motif

18. Introduction
PPIs refer to intentional physical contacts established between two or more proteins as a result of
biochemical events and/or electrostatic forces
• Proteins control and mediate many of the biological activities of cells by these interactions.
• Information about PPIs improves our understanding of diseases and can provide the basis for new
therapeutic approaches.
Practical applications include:
1.Analysis of metabolic and signal transduction;
mainly to find out disease pattern.
2. Pharmacogenetics research; the study of drug transporters,
drug receptors, and drug targets.

19. Examples of protein-protein interaction
• Signal transduction :
The activity of the cell is regulated by extracellular signals
• Transport across membranes :
A protein may be carrying another protein.
• Cell metabolism :
In many biosynthetic processes enzymes interact with each other to produce small
compounds or other macromolecules.
• Muscle contraction:
Myosin filaments act is molecular motors and by binding to enables filament sliding

21. ON THE BASIS OF THEIR COMPOSITION
• Homo-oligomers
Homo-oligomers are macromolecular
complexes constituted by only one type of
protein subunit
• Homo-oligomers complex
Protein subunits assembly is guided by
the establishment of non-covalent Interactions
in the quaternary structure of the protein
Eg. PPIs in Muscle Contraction)
Several enzymes, carrier proteins
and transcriptional regulatory factors carry out
their functions as homo-oligomers.

22. Hetero-oligomers
• Distinct protein subunits interact in hetero-oligomers, which are
essential to control several cellular functions
Eg: Hemoglobin Hb or Hgb
Heterologous proteins-cell signaling events
• Eg PPI between Cytochrome Oxidase and TRPC3 (Transient receptor
potential cation channel)

23. ON THE BASIS OF THEIR BONDING
Covalent: Strongest association - disulphide bonds or electron sharing
Post translational modifications E.g.: ubiquitination and SUMOylation
Non-covalent:
• Established during transient interactions by the combination of weaker
bonds
• Hydrogen bonds,
• Ionic interactions,
• Van der waals forces, or
• Hydrophobic bonds

24. ON THE BASIS OF THEIR DURATION OF
INTERACTION
• Transient Interaction:
Interaction that last a short period of time reversible manner.
E.g G protein coupled receptors only transiently bind Gi/o Proteins when
they are activated by extracellular ligands
• Stable Interactions:
• Proteins-interact for a long time, taking part of permanent complexes as
subunits and carry out functional and structural roles
• E.g Cytochrome C

25. PPI
DATABASES

26. • BIND ( Biomolecular Interaction Network Database)
• DIP (Database of Interacting Proteins)
• IntAct (IntAct Molecular Interaction Database)
• BioGRID (The Biological General Repository for Interaction Datasets)
• MINT (The Molecular INTeractions Database)
• HPRD (Human Protein Reference Database)
PATHWAY DATABASES
• KEGG (Kyoto Encyclopedia of Genes and Genomes)
• STRING (Search Tool for the Retrieval of Interacting Genes/Proteins)

36. STRING(SEARCH TOOL FOR THE RETRIEVAL OF
INTERACTING GENES/PROTEINS)
• STRING is a database of known and
predicted protein-protein interactions.
• COVERAGE
STRING database currently covers
24'584'628 proteins from 5'090 organisms.

47. CONCLUSION
• The identification of motifs and domains in
proteins is an important aspect of the
classification of protein sequences and functional
annotation.
• In conclusion, protein-protein interactions are of
central importance for virtually every process in a
living cell.
• Information about these interactions improves
our understanding of diseases and can provide
the basis for new therapeutic approaches.

48. Thank you very much