6.2
Protein-Protein Interfaces
Many biological processes depend on protein-protein interactions. In fact, a large number of proteins need to form protein complexes or oligomers to carry out their functions.
Sometimes, two or more identical proteins form a complex, such as this kinesin dimer. In other cases, different proteins or polypeptides come together to form a functional unit.
For example, the cytoskeletal microtubules consist of alpha- and beta-tubulin dimers. The binding surfaces of alpha- and beta-tubulin monomers have complementary shapes.
These matching shapes enable the monomers to form a large number of non-covalent bonds with each other, which then hold the alpha- and beta-tubulin together. This type of interface is an example of a surface-surface interaction.
Similar to ligand binding sites, interactions at a protein-protein interface may involve non-covalent bonds and hydrophobic forces. However, covalent disulfide bonds between cysteine amino acids on each protein surface may also play a role to keep them together.
Yet, not all protein interfaces involve closely-matching surfaces. For instance, many enzymes, such as protein kinase A here, form a cleft that can recognize and bind polypeptide loops of their binding partners. This type of interface is known as surface-string interaction.
Another type of interface, known as helix-helix, or coiled-coil interaction, forms when helices of two proteins wrap around each other. This interface is observed frequently in proteins that contain leucine zipper domains such as eukaryotic transcription factors.
In conclusion, the physical structure and chemical properties of the interacting parts determine the type of interface between two proteins.
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide chain or string.
Various computational and biochemical methods are used to study protein interfaces. Laboratory methods, such as affinity purification, mass spectrometry, and protein microarrays, can be used to identify new interactions. Co-immunoprecipitation of proteins and yeast two-hybrid screening are widely used to provide evidence on whether two proteins interact in vitro. Computer programs can predict PPIs based on similar interactions found in other proteins by comparing protein sequences and three-dimensional structures. Other computational approaches, such as phylogenetic profiling, predict PPIs based on the coevolution of binding partners. Additionally, gene fusion analysis is used to predict interaction partners by finding protein pairs that are fused in the genome of other organisms.
Proteins typically interact with multiple partners either at the same or different times, and they may contain more than one interaction interface. Many proteins form large complexes that perform specific functions that can only be carried out by the complete complex. In some cases, these protein interactions are regulated; that is, a protein may interact with different partners based on cellular needs. Further computational and statistical analyses sort such interactions into networks, which are curated in online interactome databases. These searchable databases enable users to study specific protein interactions, as well as design drugs that can enhance or disrupt interactions at the interface.
Many biological processes depend on protein-protein interactions. In fact, a large number of proteins need to form protein complexes or oligomers to carry out their functions.
Sometimes, two or more identical proteins form a complex, such as this kinesin dimer. In other cases, different proteins or polypeptides come together to form a functional unit.
For example, the cytoskeletal microtubules consist of alpha- and beta-tubulin dimers. The binding surfaces of alpha- and beta-tubulin monomers have complementary shapes.
These matching shapes enable the monomers to form a large number of non-covalent bonds with each other, which then hold the alpha- and beta-tubulin together. This type of interface is an example of a surface-surface interaction.
Similar to ligand binding sites, interactions at a protein-protein interface may involve non-covalent bonds and hydrophobic forces. However, covalent disulfide bonds between cysteine amino acids on each protein surface may also play a role to keep them together.
Yet, not all protein interfaces involve closely-matching surfaces. For instance, many enzymes, such as protein kinase A here, form a cleft that can recognize and bind polypeptide loops of their binding partners. This type of interface is known as surface-string interaction.
Another type of interface, known as helix-helix, or coiled-coil interaction, forms when helices of two proteins wrap around each other. This interface is observed frequently in proteins that contain leucine zipper domains such as eukaryotic transcription factors.
In conclusion, the physical structure and chemical properties of the interacting parts determine the type of interface between two proteins.
- Protein-protein interactions - Occur when two or more proteins bind together.
- Protein-protein complexes - Groups of proteins having interactions and functions as an entity.
- Protein-protein interface - The area where two proteins interact with each other.
- Protein interaction partners - Proteins that interact with each other in a biological system.
- Complexes in biology - Structures made up of interdependent biological entities.
- Define Protein-protein interactions – Explain where and how proteins bind together (e.g., protein-protein interactions).
- Contrast Protein-protein complexes vs Protein-protein interface – Explain the difference between the two (e.g., function and location).
- Explore Examples of Protein interaction partners – Describe how proteins interact in a system (e.g., in a cellular environment).
- Explain the Mechanism of Complexes in biology – Understand how multiple entities form complexes.
- Apply in Context Protein-protein interactions – Learn about the crucial role they play in biological systems.
- [Question 1] What are protein-protein interactions and how do they occur?
- [Question 2] What is the difference between protein-protein complexes and protein-protein interface?
- [Question 3] How do protein interaction partners function in a biological system?
From Chapter 6:
Now Playing
6.2 : Protein-Protein Interfaces
Protein Function
3.8K Views
6.1 : Ligand Binding Sites
Protein Function
6.4K Views
6.3 : Conserved Binding Sites
Protein Function
1.2K Views
6.4 : Cofactors and Coenzymes
Protein Function
8.8K Views
6.5 : Cooperative Allosteric Transitions
Protein Function
1.9K Views
6.6 : Protein Kinases and Phosphatases
Protein Function
3.4K Views
6.7 : GTPases and their Regulation
Protein Function
2.7K Views
6.8 : Covalently Linked Protein Regulators
Protein Function
1.3K Views
6.9 : Protein Complexes with Interchangeable Parts
Protein Function
1.1K Views
6.10 : Mechanical Protein Function
Protein Function
1.8K Views
6.11 : Structural Protein Function
Protein Function
2.7K Views
6.12 : Protein Networks
Protein Function
2.1K Views