POST-TRANSLATIONAL MODIFICATIONS (PTMs)

Why do PTMs often cause disease?

Writer/eraser mutations corrupt decision-making in signalling

Give an example of PTM-driven disease

Hyperactive kinases cause cancer; faulty phosphatases induce over-signalling

How do pathogens exploit PTMs?

Viruses mimic or block PTMs to shut immune responses off

Why are PTM enzymes drug targets?

Blocking a single enzyme can reset entire signalling branches

How do PTMs affect localisation?

Marks recruit transport machinery or expose signal peptides

Why do PTMs regulate stability?

Degradation removes proteins at the right time and resets pathways

How do PTMs control protein networks?

Modification changes binding to scaffolds

Why are PTMs key for signalling?

Allow reversible

Why can PTMs encode complex information?

Proteins can carry multiple marks acting together

What is PTM crosstalk?

One modification influencing the addition or removal of another

Give an example of PTM crosstalk

Phosphorylation priming ubiquitination (e.g.

Why does crosstalk matter?

Creates fine-tuned control and decision points

How can PTMs form logic gates?

Multiple marks required for a response (e.g.

What are PTM writers?

Enzymes that add chemical modifications to proteins

Give examples of writers

Kinases

What are PTM erasers?

Enzymes that remove PTMs

Give examples of erasers

Phosphatases

What are PTM readers?

Proteins that recognise and bind modified residues

Give an example of reader domain

SH2 domain binding phospho-tyrosine

Why do cells need readers?

Readers interpret signals created by writers to propagate downstream effects

Why is modular architecture efficient?

Different marks can be added

What is acetylation?

Addition of an acetyl group to lysines

Which proteins are classical acetylation targets?

Histones

What enzyme group acetylates histones?

Histone acetyltransferases (HATs)

How does acetylation affect chromatin?

Loosens chromatin packing → increases transcription

Which enzymes remove acetyl groups?

Histone deacetylases (HDACs)

How does deacetylation affect chromatin?

Tightens chromatin → represses transcription

Why is acetylation reversible?

Allows dynamic control of gene accessibility

What diseases involve HDAC activity?

Cancer and neurodegeneration

Name a drug targeting acetylation

HDAC inhibitors used as anti-cancer agents

What is ubiquitin?

A small protein tag added to lysines on target proteins

What is ubiquitination used for?

Marking proteins for degradation or altering their signalling roles

Which complex performs proteasomal targeting?

SCF ubiquitin ligase complex

What are the three enzymes in ubiquitin transfer?

E1 activating

Which enzyme gives substrate specificity?

E3 ubiquitin ligases

Where do ubiquitinated proteins go?

Proteasome for degradation

How does polyubiquitin differ from monoubiquitin?

Poly-Ub targets degradation; mono-Ub alters function/localisation

Why is ubiquitin crucial in cell cycle?

Removes cyclins and CKIs to enforce phase transitions

What is phosphorylation?

Addition of phosphate to serine

Which enzymes add phosphate groups?

Protein kinases

Which enzymes remove phosphate groups?

Protein phosphatases

Why is phosphorylation fast?

Uses abundant ATP and does not require protein synthesis

How does phosphorylation regulate activity?

Causes conformational change

Why is phosphorylation useful for signalling?

It is reversible

What do CDKs phosphorylate?

Substrates controlling cell cycle transitions

What is an example of phosphorylation cascade?

MAPK pathway Raf → MEK → ERK

Why is multisite phosphorylation powerful?

Allows digital switch-like responses from graded inputs

What is a post-translational modification?

A chemical modification added to a protein after translation

Why are PTMs important?

They rapidly change protein function without altering DNA or RNA

What do PTMs control?

Protein activity

Why are PTMs reversible?

Allows fast on/off regulation to adapt to changing signals

What determines which proteins get modified?

Enzymes that “write” marks and protein motifs that recruit them