Post-translational modifications (PTMs) are chemical changes that happen to proteins after they're made. These tweaks can totally change how a protein works, where it goes, and how long it lasts in the cell. It's like giving proteins superpowers or new jobs.

There are lots of different PTMs, like adding phosphates, sugars, or other proteins. Each type has its own special effects. PTMs play a huge role in how cells work and can even be involved in diseases. Scientists are now trying to use PTMs to make new treatments and diagnose illnesses.

Post-Translational Modifications: Types and Biological Significance

Types of post-translational modifications

• Phosphorylation attaches phosphate groups to serine, threonine, or tyrosine residues reversibly introducing negative charge (ATP-dependent kinases)
• Glycosylation links sugar moieties to proteins N-linked to asparagine or O-linked to serine/threonine (ER and Golgi apparatus)
• Ubiquitination covalently attaches ubiquitin protein to lysine residues mono- or poly-ubiquitination (E1, E2, E3 enzyme cascade)
• Acetylation adds acetyl groups to lysine residues neutralizing positive charge (histone acetyltransferases)
• Methylation appends methyl groups to lysine or arginine residues mono-, di-, or tri-methylation (methyltransferases)
• SUMOylation attaches small ubiquitin-like modifier proteins similar to ubiquitination but with distinct functions (SUMO-specific E1, E2, E3 enzymes)

Biological significance of PTMs

• Altering protein activity phosphorylation activates/inhibits enzymes acetylation changes DNA-binding of transcription factors
• Modifying protein-protein interactions phosphorylation creates/disrupts binding sites ubiquitination mediates recognition
• Changing protein localization SUMOylation alters nuclear-cytoplasmic shuttling lipidation targets proteins to membranes (prenylation)
• Regulating protein stability ubiquitination targets proteins for degradation glycosylation increases stability
• Modulating protein structure disulfide bond formation affects tertiary structure glycosylation influences folding and solubility

PTMs in cellular processes

• Signal transduction phosphorylation cascades in kinase pathways (MAPK, PI3K/AKT) allow rapid signal propagation/termination
• Protein degradation ubiquitin-proteasome system for targeted breakdown phosphorylation creates E3 ligase recognition sites
• Gene expression regulation histone modifications affect chromatin structure RNA polymerase II phosphorylation regulates transcription
• Cell cycle control cyclin-dependent kinase phosphorylation drives progression APC/C-mediated ubiquitination ensures proper mitotic timing
• Protein trafficking glycosylation directs proteins through secretory pathway SUMOylation influences nuclear import/export

PTMs in disease and therapy

• Cancer aberrant phosphorylation in oncogenic signaling (RAS/RAF/MEK/ERK) dysregulation of histone modifications in epigenetics
• Neurodegenerative diseases tau hyperphosphorylation in Alzheimer's abnormal ubiquitination in Parkinson's (α-synuclein)
• Diabetes impaired insulin receptor phosphorylation advanced glycation end-products in complications
• Autoimmune disorders citrullination of proteins in rheumatoid arthritis altered glycosylation patterns in lupus
• Therapeutic strategies targeting PTMs:
  1. Kinase inhibitors for cancer (imatinib, erlotinib)
  2. Histone deacetylase inhibitors for various cancers (vorinostat)
  3. Proteasome inhibitors for multiple myeloma (bortezomib)
  4. Glycosylation-based vaccines for infectious diseases (pneumococcal vaccines)
• PTMs as biomarkers phosphorylated tau for Alzheimer's glycosylated hemoglobin (HbA1c) for diabetes monitoring