006 Código Genético e Tradução.pdf

7/29/2019 006 Cdigo Gentico e Traduo.pdf

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05.Genetic code and Translation


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mRNA export to the cytoplasm


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Reticulocyte lysates

. Prepared from red blood cells (no nucleus)

. Large quantities of Ribosomes

. tRNAs

. rNTPs

. ATP

. mRNA haemoglobin


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O Cdigo Gentico

- cada 3 nucleotideos = 1 codo

- Conjunto de codes = Quadro de leitura (Open Reading Frame ORF)- 64 codes (4 x 4 x 4) = 61 para aminocidos

3 codes STOP

- Cdigo gentico e Universal- Codes so seguidos sem interupo- degenerado = + do que 1 codo para a maior parte dos aminocidos- Codes especfico de iniciao = AUG- Codes especficos de terminao = UAG (Amber); UAA (Ocare); UGA (Opal)


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8 grupos de codes com os primeiros dois nucletidos idnticos e o terceiro pode ser qualquer um7 pares de codes em que os dois primeiros so iguais e o terceiro e uma pirimidina (C,T,U)5 pares de codes em que os dois primeiros so iguais e o terceiro e uma purina (A,G)2 codes que so especficos3 codes em que no tem amino cido associado

5 3


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O Codigo gentico


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Quadro de leitura (Open reading frame ORF)

5' 3' !ATGCCCAAGCTGAATAGCGTAGAGGGGTTTTCATCATTTGAGGACGATGTATAA!TACGGGTTCGACTTATCGCATCTCCCCAAAAGTAGTAAACTCCTGCTACATATT!3 ! ! ! ! ! !5!

1ATG CCC AAG CTG AAT AGC GTA GAG GGG TTT TCA TCA TTT GAG GAC GAT GTATAA!M P K L N S V E G F S S F E D D V *!

2 TGC CCA AGC TGAATA GCG TAG AGG GGT TTT CAT CAT TTG AGG ACG ATG TAT !C P S * I A * R G F H H L R T M Y!

3 GCC CAA GCT GAATAG CGT AGA GGG GTT TTC ATC ATT TGAGGA CGA TGT ATA!A Q A E * R R G V F I I * G R C I !

5

5


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Quadro de leitura (Open reading frame ORF)

5


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Alteraes no cdigo gentico na mitocndria

Mitorcndria - Fosforilao oxidativa

- Genoma circular 16,000 pb

- Materno


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Alteraes no cdigo gentico

- UGA STOP=Triptofano- Metionina Interna = AUG e AUA- Metionina iniciadora = AUG;AUA;AUU;AUC- Codes STOP = UAA;UAG;AGA;AGG


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Traduo: overview


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t-RNAs


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t-RNA synthetases

Transfer RNA (tRNA) is the 'adaptor' molecule that enables the Genetic Code contained in the nucleotide sequence of a messenger RNA (mRNA) molecule to be translated into the amino acid sequence of a polypeptide chain. The key to this process lies in the specific recognition of the correct tRNA molecule by an aminoacyl-tRNA synthetase enzyme which attaches the correct amino acid for the tRNA to the acceptor stem at the 3' end of the molecule.

Humanos 500 tRNA genesS 48 codes representados


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Existem so 48 tRNAs embora o cdigogentico tem 64 codes. (61 funcionais)

Emparelhamento wobble permite a terceirabase do anticodo na posio 5 um

emparelhamento imperfeito

Wobble pairing 3 end mRNA


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Bases modificadas presentes em tRNAs


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Aminoacyl-tRNA synthetases from all organisms belong to one of two classes depending on the amino acid they are responsible for. Class I enzymes are generally (though not always) monomeric, and attach the carboxyl of their target amino acid to the 2' OH of adenosine 76 in the tRNA molecule. Class II enzymes are generally dimeric or tetrameric, and attach their amino acid to the 3' OH of their tRNA, except for phenylalaninyl-tRNA synthetase which uses the 2'

t-RNA synthetases


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Most cells make twenty different aminoacyl-tRNA synthetases, one for each type of amino acid. These

twenty enzymes are widely different, each optimized for function with its own particular amino acid and the set of tRNA molecules appropriate to that amino acid. The one shown here, which charges aspartic acid onto the proper tRNA (entry 1asz), is a dimer of two identical subunits (colored blue and green, the two tRNA molecules are colored red). Others are small monomers or large monomers, or dimers, or even tetramers of one or more different types of subunits.

t-RNA synthetases


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Aminoacyl-tRNA-synthetases

Ativao do aa

Transferncia do aa para o tRNA


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Aminoacil-tRNA sintetasas


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Controlo de qualidade


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Iniciao da traduo requer um tRNA especfico


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Ribosome structure


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Os rRNAs determinam a estrutura dos ribossomas


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Prokaryotic translationInitiation

So Formil-Met tRAN pode entrar noSite E


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Iniciao


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Eucaryotic translationinitiation


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Elongao


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Atividade peptidil-transferase

Transferncia do aa para o prximo tRNA no enzimtico. Depende do fato que oaa C-terminal foi ativado o que favorece a sua ligao ao prximo aa-tRNA


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Proofreading translation

Elongation factor-GTP


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Translation termination and releasing factors

Molecular mimicry


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Polyribosomes


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INHIBITOR SPECIFIC EFFECT

Acting only on bacteria

Tetracycline blocks binding of aminoacyl-tRNA to A-site of ribosomeStreptomycin prevents the transition from initiation complex to chain-elongating ribosome and

also causes miscodingChloramphenicol blocks the peptidyl transferase reaction on ribosomesErythromycin blocks the translocation reaction on ribosomesRifamycin blocks initiation of RNA chains by binding to RNA polymerase

Acting on bacteria and eucaryotes

Puromycin causes the premature release of nascent polypeptide chains by its addition togrowing chain end

Actinomycin D binds to DNA and blocks the movement of RNA polymerase (prevents RNAsynthesis)

Acting on eucaryotes but not bacteria

Cycloheximide blocks the translocation reaction on ribosomes (step 3 in Figure 6-65)Anisomycin blocks the peptidyl transferase reaction on ribosomes (step 2 in Figure 6-65)-Amanitin blocks mRNA synthesis by binding preferentially to RNA polymerase II

The ribosomes of eucaryotic mitochondria (and chloroplasts) often resemble those of bacteria in their sensitivity to inhibitors.Therefore, some of these antibiotics can have a deleterious effect on human mitochondria.


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Codon bias


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Abnormally folded proteinsaggregate and precipitate

Protein folding

Incorrectly folded proteins precipitate

B-amyloid


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Abnormally folded proteins are rapidly degraded

006 Código Genético e Tradução.pdf

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