Pendahuluan Biologi Molekuler
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Transcript of Pendahuluan Biologi Molekuler
Pendahuluan Biologi Molekuler
Mathematical Biosciences Institute (Ohio State Univ), 2 October 2003
RNA
Protein
DNADOGMA CENTRAL
Dogma central Biologi Molekuler
Adapted from http://www.bioinfbook.org/
DNA Sequence(splited by
genes)
RNA fenotipproteinAsam amino
DNA
Fosfat
Basa (A,T, C or G)
Gula
• DNA adalah komponen yang tersusun dari dari molekul-molekul yang disebut nukleotid
• Masing-masing nukleotid mengandung fosfat, gula dan basa nitrogen.
• Ada empat basa: Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)
DNA: structure• Ikatan gula-fosfat pada nukleotid
merupakan backbone dari ikatan pada DNA
• Empat basa dari DNA dibentuk sepanjang “backbone” disebut dengan DNA sequence.
• Dua DNA saling berikatan di antara pasangan basa
• Dua ikatan basa yang mungkin yaitu: • A-T, C-G. • Dua untai DNA mempunyai formasi
struktur double helixTwo.
Source of diagram: http://www.cs.utexas.edu/users/s2s/latest/dna1/src/page2.html
DNA: tersusun dalam kromosom
Each chromosome is essentially a package for a very long, continuous DNA double strand.
Lodish et al. Molecular Biology of the Cell (5th ed.). W.H. Freeman & Co., 2003.
DNA: di-splid oleh gen-gengene
promoter Exon 1 Exon 2 Exon 3Intron 1 Intron 2
• Gen merupakan bagian dari DNA yang membawa informasi untuk membentuk protein.
• 2-3% dari DNA manusia adalah gen, gen yang tidak aktif (rest) disebut junk DNA
• Promotor terlelak di bagian awal dari komponen gen. Promotor aktif saat gen akan bekerja.
• Pada banyak gen euryotic, gen adalahsekuen DNA yang mempunyai kode, yang juga disebut sebagai exon. Bagian yang tidak membawa kode genetik disebut sebagai intron.
RNA
Source of diagram: http://en.wikipedia.org/wiki/RNA
• RNA (ribonucleic acid) adalah intermediet antara DNA dan protein.
• RNA merupakan single strand dari asam nukleat.
• Basa nitrogen T (Thymine) pada RNA terganti oleh U (Uracil)
• Tidak seperti DNA, yang terlokasi di inti, RNA juga dapat ditemukan di sitoplasma.
• Pada inti, kode gen ditranskripsikan pada RNA. Selanjutnya RNA akan keluar dari inti ke nukleus dalam sitoplasma, dimana RNA ditranslasi menjadi asam amino.
Another view of central dogma
Gen diekspresikan pada 3 step:
1) Transkripsi: Sintesis RNA
2) Splicing: penghilangan intron dari RNA
3) Translasi: Sintesis Protein
Transkripsi• Transkripsi diinisiasi oleh kompleks dari
faktor=faktor transkripsi yang berikatan dengan promotor.
• An enzyme, RNA polymerase II, travels along the gradually unzipped DNA template and polymerizes nucleotides into an RNA.
• The sequence of nucleotides on DNA template determines the sequence on RNA by following the rule of base-pair complementarity, i.e., A – U, T- A, C – G, G – C.
• Transcription continues until entire gene is
copied to RNA.
Source of diagram: http://ghs.gresham.k12.or.us/science/ps/sci/ibbio/chem/nucleicAnimation
Splicing
pre mRNAExon 1 Exon 2 Exon 3Intron 1 Intron 2
mature mRNA
Translation (1)• By translation, the nucleotide
sequence on mRNA
determines the amino acid sequence by genetic code.• Genetic code: three base pairs of
RNA (called a codon) determine one amino acid based on a fixed table.
• Translation always starts at AUG (start codon), and ends with any of UAA, UAG, or UGA (stop codon)
Translation (2) Transfer RNAs (tRNAs): small RNA
molecules. Most of the tRNAs function as carriers of amino acids and participate in protein synthesis.
For example, the tRNA with the anticodon CGG corresponds with the codon GCC and attaches alanine amino acid onto the peptide chain.
Ribosome: a complex of protein and rRNA
Animation
Source of diagram: http://www.wiley.com/legacy/college/boyer/0470003790/structure/tRNA/
SummaryCentral dogma of molecular biology
Three components DNARNAProtein
Three steps transcriptionsplicingtranslation
Cell – cell communication
A process by which signals from outside the cell are transferredinside the cell through cascade of proteins interaction. Involved in all cellular activities (death, growth, differentiation, etc.)
Regulate by protein phosphorylation.
Cellular signal transduction
Proto-oncogenes
encode components
of growth factor signal transduction
pathways
Components shown in yellow are known proto-oncogenes
The VEGF family and its receptors
Adapted from Ferrara N. Nat Med 2003;9:669–76
Migration, permeability, DNA synthesis, survival
Lymphangiogenesis
– P– PP–
P–
– P– P
P– P–
– P– P
P– P–
VEGF-AVEGF-B
PlGF
VEGF receptor-1
VEGF-A
VEGF receptor-2
VEGF-CVEGF-D
VEGF receptor-3
Angiogenesis
VEGF signal transduction and its effects
Shibuya M. Cell Struct Funct 2001;26:25–35
VEGF binding to VEGF receptor-2 activates a signalling cascade resulting in cellular effects
Cation channel
Permeability
– P– PP–
P–
– P– P
P– P–
– P– P
P– P–
VEGFVEGF receptor-1
VEGF
VEGF receptor-2
VEGF-CVEGF-D
VEGF receptor-3
DAGDAG
PLCPLC
Protein kinase C Raf-1 MAPK
Proliferation, migration Permeability
SAPK/ JNK
ApoptosisSurvival
Calcium release
Ca2+
ProliferationMigration
IP3
PLC
P13K
Protein kinase B
Agents targeting theVEGF pathway
VEGFVEGF
receptor-2
Cation channel
PermeabilityAntibodies inhibiting VEGF
(e.g. bevacizumab)
Antibodies inhibiting VEGF receptors Soluble VEGF receptors
(VEGF-TRAP)
Small-molecules inhibiting VEGF receptors (TKIs)(e.g. PTK-787)
Ribozymes(Angiozyme)
– P– PP–
P–
– P– P
P– P–
– P– P
P– P–
Migration, permeability, DNA synthesis, survival
Lymphangiogenesis
Angiogenesis
GDPSos
Grb2
P PGTP
GTP
Ras
Growth factor
P120-GAP Neurofibro
min14-3-3
1 23
14-3-31 2
3Inactive Raf
14-3-31 2
3
14-3-31 2
3
Transcription factors
etc.
DNA synthesis
Nucleus
MEK
ERK1 ERK1 ?
Active Raf
P13-K
Rac and Rho
pathway
Morphological change
Ras
Signal Transduction from Receptor to Nucleus Via RAS p21
Regulators : proliferation, differentiation, apoptosis, repair
Genome :Genes :
Cell cycleDifferentiati
oApoptosisRepairMetabolis
metc
ProteomeProtein:
cyclin, CDK,CDKI
GF : GM-CSF, FGF
Bcl-2, p53, caspase
Gadd, enzym repair
dll
Transcriptome
RNA
RNA
RNA
RNA
RNA
RNA