Graduate Biochemistry Β· The Ribosome
The Ribosome
The RNA-catalysed machine that reads the genetic code β a ribozyme 3 billion years older than the first protein enzyme it ever built.
About This Course
The ribosome is the single most abundant macromolecular assembly in the cell β ~10 million per growing bacterium, ~107 per eukaryotic cell β and the only one that synthesises itself. It translates ~20 amino acids per second per ribosome in E.Β coli; at any moment, a rapidly growing bacterium devotes 40% of its dry mass to ribosomes. Its discovery by George Palade in 1955, its resolution into 30S and 50S subunits by Osawa and Korn, its sedimentation-coefficient naming (70S, 80S), and the 2009 Nobel Prize-winning atomic structures by Ramakrishnan, Steitz, and Yonath β together the intellectual spine of this course.
Seven modules cover structure, the elongation and initiation cycles, antibiotic binding, ribosomopathies, and the surprising recent finding that ribosomes are not a single, uniform machine but a population of specialised ribosomes with tissue- and condition-specific bias.
Key Facts
Translation rate (bacteria)
~20 amino acids per second
Translation rate (eukaryote)
~5-6 amino acids per second
Error rate per codon
~10β»Β³ (1 error per ~1000 codons)
Ribosome content (E. coli)
~10β· ribosomes per cell = 40% dry mass
GTP per codon
2 GTP (EF-Tu + EF-G) + 1 ATP (tRNA charging)
Peptidyl transferase
Catalysed by 23S rRNA (ribozyme)
Seven Modules
M0
Discovery & Structure
Palade 1955 ribosomes in EM, 30S/50S and 40S/60S, Ramakrishnan/Steitz/Yonath 2009 Nobel atomic structures, the ribosome as a ribozyme.
M1
Translation Initiation
eIF1/eIF1A/eIF3 scanning, 43S preinitiation complex, start-codon recognition, eIF5B & 80S assembly, IRES-mediated initiation, uORFs.
M2
Elongation Cycle
Aminoacyl-tRNA loading via EF-Tu, decoding centre and proofreading, peptidyl transfer by the 23S rRNA, translocation by EF-G, 20 aa/s rate.
M3
Termination & Recycling
eRF1/eRF3 stop-codon recognition, ABCE1 recycling, NMD/NSD/NGD mRNA surveillance, ribosome-associated quality control (RQC).
M4
Antibiotics
Aminoglycosides (decoding), macrolides & chloramphenicol (peptidyl-transfer/exit tunnel), tetracyclines (A-site block), resistance mechanisms.
M5
Ribosomopathies
Diamond-Blackfan anaemia (RP mutations), 5q- syndrome, Shwachman-Diamond (SBDS), dyskeratosis congenita (DKC1/telomere), TCF3-HLF cancer.
M6
Specialised Ribosomes
RP paralogues, variant rRNA modifications, ribosome-associated factors, tissue-specific translation, translation during stress and differentiation.
Cross-Links
Organelles,Endoplasmic Reticulum,Molecular Biology,Biochemistry,Pharmacology.