For more information, please visit https://www.creative-proteomics.com/services/protein-protein-interaction-networks.htm. Protein-protein interactions play important roles in various biological processes. PPIs can be classified based on different factors, including composition, affinity, and lifetime.
2. Protein-Protein Interactions
Protein-protein interactions (PPIs) refer to intentional physical contacts established
between two or more proteins as a result of biochemical events and/or electrostatic
forces.
Proteins,
biomolecules or
macromolecules,
perform a wide range
of functions in
organisms.
1
Almost all of the
cellular processes
require that proteins
specifically recognize
a multitude of different
interaction partners.
2
Proteins can carry out
their roles by
interacting with other
molecules, including
DNA, RNA, proteins,
and small molecules.
3
3. Biological Effects of Protein-
Protein Interactions
1
2
PPIs can alter the kinetic properities of
enzymes, which may lead to subtle
changes in substrate binding or
allosteric effects.
PPIs can act as a general mechanism
to allow for substrate channeling by
moving a substrate between domains
or subunits.
PPIs play important roles in various biological processes, including cell-to-cell
interactions, cell cycle progression, signal transduction, and metabolic pathways.
4. Biological Effects of Protein-
Protein Interactions
3
PPIs can create a novel binding
site for small effectors molecules.
PPI can inactivate or suppress a
protein.
PPI can change the specificity of
a protein for its substrate by
interacting with different binding
partnersIn an upstream or a downstream
event, PPIs can work as a
regulatory role.
4
5
6
5. Types of the Protein-
Protein Interactions
Composition Affinity Lifetime
6. Types of the Protein-Protein
Interactions
Compositions
homo-
oligomer
PPI occurs between
identical chains
hetero-
oligomer
PPI occurs between
non-identical chains
GroEL consists of 14 identical subunits of 57 kDa each
forming two heptameric rings arranged back-to-back. A
chaperonin protein is formed by seven GroEL proteins
associating as a homo-heptamer
Several enzymes, carrier proteins, scaffolding proteins, and transcriptional
regulatory factors carry out their functions as homo-oligomers.
7. Types of the Protein-Protein
Interactions
Affinity
Obligate
Constituents (protomers, monomers)
of a complex are unstable on their
own in vivo
Non-obligate
The components of non-obligate
interactions can exist independently
Ku proteins, which are involved in DNA repair, are
shown to bind DNA as obligate homodimers.
Krishna S S, Aravind L. The bridge-region of the Ku superfamily is an atypical zinc
ribbon domain. Journal of structural biology, 2010, 172(3): 294-299.
8. Types of the Protein-Protein
Interactions
Affinity
Obligate
Constituents (protomers, monomers)
of a complex are unstable on their
own in vivo
Non-obligate
The components of non-obligate
interactions can exist independently
H-Ras protein, a G protein, can interchangeably
form non-obligate complexes with guanosine
triphosphatase (GTPase) activating proteins
(GAPs).
9. Types of the Protein-Protein
Interactions
Lifetime
Transient The components of transient interaction
associate and dissociate temporarily in vivo
Permanent Permanent interactions are usually very
stable and irreversible
10. Types of the Protein-Protein
Interactions
Acuner Ozbabacan S E, Engin H B, Gursoy A, et al. Transient protein–protein interactions. Protein engineering, design and selection,
2011, 24(9): 635-648.
• Components are stable only in complex
form.
• Association or dissociation takes place
under certain triggers.
• Complexes are broken and formed
continuously and Kd is in a micromolar range.
• The domain-peptide complexes are mostly
transient
11. Types of the Protein-Protein
Interactions
Based on lifetime
Based on affinity
Protein-Protein
Interaction
Non-obligate
Transient
Strong
transient
Weak
Transient
Permanent
Obligate
12. Protein-Protein Interactions in
Drug Development
• Targeted modulation of PPIs with small molecules is one of the most
promising approaches with more than 50 PPIs that have successfully
been targeted with small molecules.
• Most of these are inhibitors of PPIs, but stabilization of PPIs is also a
strategy for targeted PPI modulation.
13. Protein and Protein Interaction In
Drug Development
Competition Stabilization
Competitive mode of inhibition
Allosteric mode of inhibition Connectional mode of stabilization
Allosteric mode of stabilization
Compounds have different modes of action on PPIs.
14. Protein-
Protein
Interactions
Services
Our Services
01Co-immunoprecipitation
05Far-Western Blot
Analysis
02 Pull-Down Assay
03 Crosslinking Protein
Interaction Analysis
04 Label Transfer Protein
Interaction Analysis
At Creative Proteomics, our team of experts with extensive experience can help
you understand what you are trying to investigate and give you the most
appropriate solutions about protein and protein interactions.
15. Thanks For Your Listening
Please contact us for more information
Web:
Email:
www.creative-proteomics.com
info@creative-proteomics.com
Editor's Notes
compounds have different modes of action on PPIs. For PPI inhibitors, they can display a competitive effect on the PPI to prevent the binding of the natural binding partner, which was called competitive mode. Another way is by binding of a compound to a site not-directly part of the PPI interface but arresting the protein in a low-affinity conformation, so that binding of the natural binding partner is impeded. A connectional or allosteric mode of stabilization is also possible. Through binding of a compound in an allosteric mode of stabilization, a protein can bind to its natural ligand in a high-affinity conformation to enhance PPI. Another form of stabilization is the connectional mode of action, which is the direct binding in the rim of the interface with simultaneously contacting both protein partners.
At Creative Proteomics, our team of experts with extensive experience can help you understand what you are trying to investigate and give you the most appropriate solutions about protein and protein interaction. We can provide protein-protein interaction services based on different methods, including:
Co-immunoprecipitation (co-IP)
Pull-Down Assay
Crosslinking Protein Interaction Analysis
Label Transfer Protein Interaction Analysis
Far-Western Blot Analysis