Scribd Logo
Upload

Welcome to Scribd!

  • 14 views

    Screenshot 2021-10-05 at 13.33.13

    Uploaded by

    asfsd asdsfas
    Three key points were summarized: 1) Translation initiation and elongation require many factors including GTPase enzymes that induce ribosome conformational changes. 2) Inhibitors of ribosomes can be beneficial like antibiotics or harmful like pathogen toxins. 3) Genetic mutations originate from frameshift, missense, or nonsense mutations.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    Screenshot 2021-10-05 at 13.33.13

    Uploaded by

    asfsd asdsfas
    14 views17 pages
    Three key points were summarized: 1) Translation initiation and elongation require many factors including GTPase enzymes that induce ribosome conformational changes. 2) Inhibitors of ribosomes can be beneficial like antibiotics or harmful like pathogen toxins. 3) Genetic mutations originate from frameshift, missense, or nonsense mutations.

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Three key points were summarized: 1) Translation initiation and elongation require many factors including GTPase enzymes that induce ribosome conformational changes. 2) Inhibitors of ribosomes can be beneficial like antibiotics or harmful like pathogen toxins. 3) Genetic mutations originate from frameshift, missense, or nonsense mutations.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    14 views17 pages

    Screenshot 2021-10-05 at 13.33.13

    Uploaded by

    asfsd asdsfas
    Three key points were summarized: 1) Translation initiation and elongation require many factors including GTPase enzymes that induce ribosome conformational changes. 2) Inhibitors of ribosomes can be beneficial like antibiotics or harmful like pathogen toxins. 3) Genetic mutations originate from frameshift, missense, or nonsense mutations.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 17

    Part B

    Molecular Biology [012] Proteins

    DNA

    RNA
    Finn Werner
    Director, Institute of
    Structural and Molecular Biology
    UCL, London, UK
    protein
    Three languages or codes in Biology ~1960 AD

    DNA
    Jim Watson

    Francis Crick

    RNA
    The central dogma of
    molecular biology – ‘DNA makes
    RNA makes protein’
    Protein
    Mechanisms of translation

    Initiation
    - Or how to recognise the start of an open reading
    frame (ORF)
    Bacteria

    5’ AUG GGG AAA GCA UUU CUG AUG CGC ACU UCC CCC UGA 3’

    leader AUG UGA trailer

    Direct baseparing
    between ribosomal
    RNA and mRNA
    RBS

    mRNA 5’ GGAGGA(T/A)9 AUG 3’

    CCUCCU
    16S rRNA
    3’ 5’

    RBS = ribosome binding site also ‘Shine-Dalgarno’ sequence


    Eukaryotes
    5’ GGG AAA GCA CCACC AUG CGC ACU AUG UCC CCC UGA 3’

    5’ UTR AUG UGA 3’ UTR


    UTR = untranslated region

    Not facilitated by
    Kozak sequence (on mRNA) direct baseparing
    CCACCAUGG between ribosomal
    RNA and mRNA

    5’ AUG UGA AAA 3’


    cap
    mRNA
    Similar to nucleic acid polymerases
    Ribosomes require accessory factors to function
    The Other Players
    (1) Initiation factors: " IF1
    " " " " IF2 (GTPase)
    " " " " IF3
    (2) Elongation factors:" EF-Tu (GTPase)
    " " " " EF-G (GTPase)
    (3) Termination factors:" RF-1
    (Release factors)" RF-2
    " " " " RF-3 (GTPase)
    " " " " RRF (Ribosome recycling factor)

    Energy released by the hydrolysis of GTP facilitates


    conformational (structural) changes – the fuel of the engine
    Initiation

    1. mRNA CCUCC
    GGAGG AUG

    GTP
    IF3 IF1 IF2
    2. GGAGG AUG

    IF=initiation factor
    fmet GTP
    3.
    IF3 IF1 IF2
    GGAGG AUG

    30S initiation complex (mRNA+small subunit)

    GDP +Pi
    4. P A
    fmet Initiation
    E
    Factors
    GGAGG AUG released

    70S initiation complex (mRNA+small+large subunit)

    P = peptidyl-tRNA binding site


    A = aminoacyl-tRNA binding site
    E = tRNA exit site
    Mechanisms of translation

    Elongation
    - How to move along the mRNA
    Translation elongation I
    Overview of decoding and elongation I

    • tRNA-aa binds reversible as a complex with EF-Tu*GTP


    • Anticodon can interact with codon in the A-site, CCA-end
    with bound aa is bound to EF-Tu (A/T-state)
    • GDP bound EF-Tu dissociates rapidly from ribosome
    Overview of decoding and elongation
    Translation elongation II
    II
    • Accommodated tRNA*aa rapidly undergoes peptidyl-transferase
    reaction - aa added to the polypeptide chain
    • Ribosome must shift the mRNA to the 3’
    • EF-G*GTP binds to the ribosome
    • GTPase activity generates EF-G*GDP, translocates the peptidyl
    tRNA from the A to the P site and the deacylated tRNA shifts to E
    • EF-G*GDP then dissociates from the ribosome
    Mechanisms of translation
    A reoccurring theme

    Baseparing and nucleotides

    • Replication template
    • Replication energy substrates
    • Transcription template
    • Transcription energy substrates
    • Translation decoding mRNA-tRNA
    • Translation ribosome-mRNA binding
    • Translation factor energy substrates

    Nucleic acids – the deep fabric of


    biological information
    Application of the knowledge about
    ribosome structure and function
    The Good - Antibiotics fight bacterial infection

    • Antibiotics are made by funghi in nature


    • Means to eliminate ‘the competition’ for resources
    • Target vital processes in the cell
    (cell division, transcription and translation)

    tetracycline - inhibits aminoacyl-tRNA binding

    erythromycin - binds peptidyl transferase site and blocks


    polypeptide exit from ribosome

    chloramphenicol - blocks correct positioning of the


    aminoacyl-tRNA inhibits peptidyl transferase reaction
    The Bad – toxins as bioweapons and disease
    Ricin - targets eukaryotic and prokaryotic cells -
    prevents activation of translation factor GTPases

    lys GTP
    P A
    fmet X EF-Tu X
    AUG AAA GGG
    GDP +Pi
    • The umbrella murder of a Bulgarian spy in ’78
    • Breaking Bad’s Heisenberg poison
    • Recent terrorist caught by FBI for attempting to buy ricin on the internet

    Diptheria toxin - acts on a eukaryotic elongation factor


    The toxin couples ADP-ribose to the factor and inactivates it

    EF
    [012] A large array of translation factors facilitate translation initiation
    and elongation, many of which utilise GTPase activity to induce
    conformational changes such as the translocation movement of the
    ribosome along the mRNA. Inhibitors of ribosomes can be useful (eg.
    Antimicrobial antibiotics) or harmful (eg. Pathogen toxins). Genetic
    mutations can originate from frameshift, missense or nonsense
    mutations.

    You might also like