Question

How could Rb avoid innapropriate phosphorylation?

Answer 1

Answer:

Phosphorylation:

Phosphorylation of retinoblastoma protein (pRB) is happens by binding of cyclin dependent kinase (CDK) and cyclin complexes like cdk4/6-cyclin D and cdk2-cyclin E. This will prevent binding free pRb to E2F, or can occur the pRb/E2F complex to fall apart. Now that E2F is free, it can activate the progression of the cell though to S-phase. It is a specific amino acid that undergoes Phosphorylation, and has been observed to disrupt the A and B-domain binding site of pRb.

Specificity in binding: By binding to the specific sites can avoid inappropriate phosphorylation.

When pRB and E2F form a complex, pRB is activated, and leads to inhibition of cell growth. E2F having family of transcription factors E2F-1, E2F-2, E2F-3, E2F-4, and E2F-5. Specifically, E2F-1, E2F-2, E2F-3, and E2F-4 bind to retinoblastoma during the G0, Gap-1, and S stages of the cell cycle. This formed complex is held together by many weak interactions like hydrophobic interactions, hydrogen bonds and a salt bridge. The retinoblastoma protein’s active site is composed of two domains. Domains A & B which form the pRB pocket domain that E2F can bind to, the C-terminal residues on pRb are also requires for E2F to bind with a higher affinity. Specifically, E2F binds to the α4, α5, α6, α8, and α9 helices of the domain A and can only bind to the α11 helix of the domain. It also found that of the entire E2F complex only the two end regions are needed to bind pRb, the marked box region and the trans-activation domain which is composed of residues. Any point of mutations, any of the amino acids will block binding of pRb, leading to deactivation of pRb cell inhibiting function, and will allow E2F to promote the cell cycle to move on to the S-phase.

If pRB leads to dysfunctionality then immediately activates:

Activation of retinoblastoma protein occurs when it is hypophosphorylated allows bound to E2F and is not mutated. When hypo-phosphorylated, it inactivates cdk-cyclin complexes and is tightly bound to E2F. A non mutated pRb protein can undergo proper Phosphorylation and proper binding to E2F. There are also many ways to inactivate pRb, Phosphorylation of pRb, interaction with viral proteins, mutation of the pRb gene, and via the Caspade-mediated degradation.

Note: The provided answer is as per my knowledge may be or may not be 100% correct, but definitely relevant to your question thank you so much.