Protein–Protein Interactions

What defines a domain in a protein?

Distinct part of a protein that can fold and function independently of the rest of the protein.

How do domains relate to exons?

Domains often correspond to exons, reflecting gene structure.

What is unique about motifs compared to domains?

Motifs are formed by secondary structures and are not independently stable, while domains are structurally and functionally independent.

What type of protein is Fibronectin?

Fibronectin is a multidomain protein with key roles such as cell adhesion, migration, and wound healing.

What is the primary role of Fibronectin in the extracellular matrix (ECM)?

Fibronectin supports mechanical strength and elasticity in tissues.

What are the three domain types present in Fibronectin?

The three domain types in Fibronectin are FnI, FnII, and FnIII.

What is the function of the RGD motif in Fibronectin?

The RGD (Arg-Gly-Asp) motif is responsible for binding integrins.

What role do the FnI domains play in Fibronectin?

FnI domains are involved in fibronectin-fibronectin interactions and are rich in disulfide bonds.

What distinguishes the FnII domain from the other domains in Fibronectin?

The FnII domain is specifically recognized for its collagen binding capability.

What is the functional significance of FnIII domains?

FnIII domains bind integrins, can unfold under force, and expose cryptic binding sites for crosslinking.

What does 'functional elasticity' mean in the context of Fibronectin?

Functional elasticity refers to the ability of Fibronectin to undergo changes during mechanical stress and form new interactions.

What is FnBPA?

FnBPA is Fibronectin Binding Protein A from Staphylococcus aureus that binds to FnI domains using a tandem β-zipper mechanism.

How many repeats does FnBPA contain and what is their function?

FnBPA contains 11 repeats, each binding one Fn molecule to form a large complex.

What type of infections can Staphylococcus aureus cause?

Infections caused by Staphylococcus aureus include bacteremia, endocarditis, toxic shock syndrome, and MRSA.

What is a characteristic feature of intrinsically disordered proteins (IDPs)?

IDPs, including FnBPA, have unstructured regions that allow flexible binding to multiple partners.

How is Kd (dissociation constant) defined in protein interactions?

Kd measures binding strength, where a lower Kd indicates tighter binding.

What does it mean when it is stated that at Kd, half of the proteins are bound?

At Kd, half of the proteins are bound to the ligand, indicating the binding equilibrium.

What does Isothermal Titration Calorimetry (ITC) measure?

ITC measures heat changes during binding and provides values for Kd, binding stoichiometry, enthalpy, and free energy.

What is the function of Factor H in the immune system?

Factor H regulates the complement immune system and prevents immune attack on self-cells.

How does Neisseria meningitidis evade the immune system?

The protein fHbp mimics host targets to bind Factor H, achieving tight binding through shape complementarity and multiple interactions.

What are the benefits of having intrinsically disordered regions in proteins?

Intrinsically disordered regions provide large interfaces with fewer residues, are compact, and allow flexible binding.

What type of interactions contribute to the high affinity of fHbp to Factor H?

High affinity is achieved via shape complementarity, hydrogen bonding, and hydrophobic and ionic interactions.

What does the term 'Evolved high-affinity mechanisms' refer to in the context of bacterial proteins?

It refers to how bacteria have developed proteins that bind tightly to host proteins like fibronectin for successful infection.

Why is structural understanding important in characterizing protein interactions?

Structural understanding is key to characterizing protein interactions as it provides insights into their function and potential therapeutic targets.

What are the key roles associated with Fibronectin in biological processes?

Fibronectin is involved in cell adhesion, migration, wound healing, and development.

What structural characteristics define a multidomain protein like Fibronectin?

Multidomain proteins like Fibronectin have multiple distinct domains that contribute to their structural and functional diversity.

Explain how the rigidity of loops connects domains in proteins like Fibronectin.

Rigid loops connect the domains in proteins like Fibronectin, allowing for stable configuration while maintaining flexibility.

In protein function, how do amino acid sequences within intrinsically disordered regions contribute?

Amino acid sequences within intrinsically disordered regions contribute functional versatility by allowing rapid conformational changes to facilitate binding.

What is the significance of understanding protein–protein interactions in the context of pathogenesis?

Understanding these interactions is crucial as they are central to the biological functions that bacteria exploit to infect hosts.