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    Biosintesis ProteinMK. BiokimiaUniversitas Udayana

    I Nengah WirajanaEmail: [email protected]

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    Pendahuluan

    Anda telah mengetahui bagaimana DNAdireplikasi dan bagaimana DNA ditranskripsi

    menjadi RNA.

    Kita sekarang akan mempelajari mekanisme

    sintesis protein, suatu proses yang disebut

    translasikarena empat-hurup alfabet asam

    nukleat (GACT) ditranslit menjadi dua puluh

    hurup alfabet protein (20 asam amino). Translasi terjadi dalam ribosom.

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    Pendahuluan

    Protein Assembly. The ribosome, shown at the right, is a factory for the manufacture of

    polypeptides. Amino acids are carried into the ribosome, one at a time, connected to transfer RNA

    molecules (blue). Each amino acid is joined to the growing polypeptide chain, which detaches

    from the ribosome only once it is completed. This assembly line approach allows even very long

    polypeptide chains to be assembled rapidly and with impressive accuracy. [(Left) Doug

    Martin/Photo Researchers.]Sumber : 6/22/2014 3

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    Kodon

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    Codon Reading Frame

    AUG is always thestart codon so allpolypeptides beginwith Methionine

    when they aresynthesized

    Having a consistentstart codon is

    necessary so thatthe reading frameis always the same.

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    1. Translasi Urutan Nukleotida

    Menjadi Urutan asam Amino Dasar sintesis protein sama pada

    semua mahluk hidup (all kingdoms of

    life), menunjukkan fakta bahwa sistem

    sintesis protein muncul paling awaldalam evolusi.

    Protein disintesis dalam arah dari

    amino-ke-karboksil, denganpenambahan secara berurutan asam

    amino pada ujung karboksil dari rantai

    peptida yang sedang tumbuh (lihatGambar berikut .6/22/2014 7

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    1. Translasi Urutan Nukleotida Menjadi Urutan asam Amino

    Pertumbuhan rantai polipeptida. Protein

    disintesis dengan penambahan berurutan

    asam amino pada terminal/ujung karboksil.

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    1.1. The Synthesis of Long Proteins Requires a

    Low Error Frequency

    The process of transcription is analogousto copying, word for word, a page from abook.

    There is no change of alphabet orvocabulary; so the likelihood of a changein meaning is small.

    Translating the base sequence of anmRNA molecule into a sequence of aminoacids is similar to translating the page of a

    book into another language. Translation is a complex process,

    entailing many steps and dozens ofmolecules. The potential for error exists at

    each step. 6/22/2014 9

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    1.1. The Synthesis of Long Proteins Requires a

    Low Error Frequency

    The complexity of translation creates a conflictbetween two requirements: the process must be not

    only accurate, but also fast enough to meet a cell's

    needs.

    How fast is "fast enough"? In E.coli, translation takesplace at a rate of 40 amino acids per second, a truly

    impressive speed considering the complexity of the

    process.

    How accurate must protein synthesis be? Let us

    consider error rates. The probabilityp of forming a

    protein with no errors depends on n, the number of

    amino acid residues, and e, the frequency of insertion

    of a wrong amino acid:

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    1.1.The Synthesis of Long Proteins Requires a Low Error Frequency

    Table 1. Accuracy of protein synthesis

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    Jelaskan arti persamaan dan tabel di atas!

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    1.2. Transfer RNA Molecules

    Have a Common Design

    The fidelity of protein synthesis requires theaccurate recognition of three-base codons onmessenger RNA.

    Recall that the genetic code relates each amino

    acid to a three-letter codon. An amino acid cannot itself recognize a codon.

    Consequently, an amino acid is attached to aspecific tRNA molecule that can recognize thecodon by Watson-Crick base pairing.

    Transfer RNA serves as the adapter moleculethat binds to a specific codon and brings with itan amino acid for incorporation into thepolypeptide chain.

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    1.3. The Activated Amino Acid and the Anticodon

    of tRNA Are at Opposite Ends of

    the L-Shaped Molecule

    The most important properties of the tRNA structure are:

    1. The molecule is L-sh aped (Figur e 29.5).

    2. There are two apparent ly co nt inuou s segments o f dou ble helix .These segments are l ike A-form DNA, as expected fo r an RNAhelix . The base-pairing predicted from the sequence analysis is

    correct. The helix containing the 5 and 3 ends stacks on top of thehelix that ends in the TyC loop to form one arm of the L; theremaining two helices stack to form the other (Figure 29.6).

    3. Most of the bases in the nonhelical regions participate inhydrogenbonding interactions, even if the interactions are notlike those in Watson-Crick base pairs.

    4. The CCA terminus containing the amino acid attachment site

    extends from o ne end o f the L. This sing le-stranded region canchange conformation during amino acid activation and proteinsynthesis.

    5. The anticodon loop is at the other end of the L, makingaccessible the three bases that make up the anticodon.

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    1.3. The Activated Amino Acid and the Anticodon of tRNA Are at Opposite

    Ends of the L-Shaped Molecule

    Figure 29.4. General Structure of tRNA Molecules. Comparison of the basesequences of many tRNAs reveals a number of conserved features.

    29.5. L-Shaped tRNA Structure. A skeletal model of yeast phenylalanyl-tRNA revealsthe L-shaped structure. The CCA region is at the end of one arm, and the anticodon loopis at the end of the other.

    Figure 29.6. Helix Stacking in tRNA. The four helices of the secondary structure oftRNA (see Figure 29.4) stack to form an L-shaped structure.

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    2. Aminoacyl-Transfer RNA Synthetases

    Read the Genetic Code

    The linkage of an amino acid to a tRNA is crucial fortwo reasons. First, the attachment of a given amino acid to a particular

    tRNA establishes the genetic code. When an amino acidhas been linked to a tRNA, it will be incorporated into agrowing polypeptide chain at a position dictated by theanticodon of the tRNA.

    Second, the formation of a peptide bond between freeamino acids is not thermodynamically favorable. Theamino acid must first be activated for protein synthesis to

    proceed. The activated intermediates in protein synthesis are

    amino acid esters, in which the carboxyl group of anamino acid is linked to either the 2 - or the 3 -hydroxylgroup of the ribose unit at the 3 end of tRNA.

    An amino acid ester of tRNA is called an aminoacyl-tRNAor sometimes a charged tRNA.6/22/2014 15

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    2.1. Amino Acids Are First

    Activated by Adenylation

    The activation reaction is catalyzed by specific

    aminoacyl-tRNA synthetases, which are also called

    activating enzymes.

    The first step is the formation of an aminoacyladenylate from an amino acid and ATP.

    This activated species is a mixed anhydride in which

    the carboxyl group of the amino acid is linked to the

    phosphoryl group of AMP; hence, it is also known as

    aminoacyl-AMP.

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    The next step is the transfer of theaminoacyl group of aminoacyl-AMP to a

    particular tRNA molecule to form

    aminoacyl-tRNA.

    The sum of these activation and transfersteps is

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    Post Translation

    Protein structure is determined byamino acid sequence and modifications

    Modifications include

    The attachment of certain sugars, lipids, orphosphate groups

    Joining different subunits of the protein to

    create the quaternary structure

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    Point Mutations

    The change of a single nucleotide in the

    DNAs template strand

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    Two Types of Mutation

    Substitutions

    Replacing one or more base with others

    Insertions or DeletionsAdding or removing one or more base

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    Terima kasih,

    Selamat belajar.

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