central dogma: the story of life rna dna protein
TRANSCRIPT
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Central dogma: the story of life
RNA
DNA
Protein
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Proteomics
Lecture 1Introduction to Proteomics and
Protein ChemistryBy Ms Shumaila Azam
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DNA structure
Atomic structure Double helix
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The basic unit in DNA
AT GC
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From DNA to Protein
1. Transcription
2. Translation
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Step1: Transcription, generation of mRNA
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Amino acid carrier: tRNA
Step2: Translation, protein assembly
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Peptide bond formation
Peptide Chain
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Protein structure
Primary
SecondaryTertiary
Quaternary
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The bonds contribute to protein structure
1. Hydrogen bond
2. Hydrophobic interaction
3. Ionic bond
4. Disulfide bond
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Proteins are the molecule tools for most cellular functions
TYPE FUNCTION EXAMPLE Structural proteins Support Collagen, Elastin,
Keratin Storage proteins Storage of amino acid Ovalbumin,
Casein Transport proteins Transport of other
substrate Hemoglobin
Hormonal proteins Coordination of and organism’s activities
Insulin
Receptors proteins Response of cell to chemical stimuli
Receptor in nerve transmit route
Contractile proteins Movement Actin, Myosin Defensive proteins Protecton against
disease Antibodys
Enzymatic proteins Selective acceleraton of chemical reactions
Trypsin, ATPase, GAPDH
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What is “bioinformatics”?
Let’s take minutes to see the hot topic” bioinformatics
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What is “bioinformatics”?
(Molecular) Bio – informatics
One idea for a definition?
Bioinformatics is conceptualizing biology in terms of molecules (in the sense of physical-chemistry) and then applying “informatics” techniques (derived from disciplines such as applied math and statistics) to understand and organize the information associated with these molecules, on a large-scale.
Bioinformatics is “MIS” for Molecular Biology Information. It is a practical discipline with many applications.
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Bioinformatics - History
1980
2005
2000
1990
1985
1995
Single StructuresModeling & GeometryForces & SimulationDocking
Sequences, Sequence-Structure Relationships
AlignmentStructure PredictionFold recognition
GenomicsDealing with many sequencesGene finding & Genome Annotation Databases
Integrative AnalysisExpression & Proteomics DataData miningSimulation again….
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Introduction to proteomics
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What’s “proteomics” ?
"The analysis of the entire protein complement
expressed by a genome, or by a cell or tissue
type.“
Two most applied technologies:
1. 2-D electrophoresis: separation of complex protein mixtures
2. Mass spectrometry: Identification and structure analysis
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Why proteomics becomes an important discipline
Significant DNA sequencing results: 45 microorganism genomes have been sequenced and
170 more are in progress 5 eukaryotes have been completed
Saccharomyces cerevisiae Schizosaccharomyces pombe Arabodopsis thaliana Caenorhabditis elegans Drosophilia melanogaster Rice, Mouse and Human are nearly done
However, 2/3 of all genes “identified” have no known function
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Only DNA sequence is not enough
Structure Regulation Information
Computers cannot determine which of these 3 roles DNA play solely based on sequence (although we would all like to believe they can)
Those are what we need to know about proteins
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Introduction to Proteomics
Definitions 1. Classical - restricted to large scale analysis of
gene products involving only proteins (small view) 2. Inclusive - combination of protein studies with
analyses that have genetic components such as mRNA, genomics, and yeast two-hybrid (bigger view)
Don’t forget that the proteome is dynamic, changing to reflect the environment that the cell is in.
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1 gene = 1protein?
1 gene is no longer equal to one protein
The definition of a gene is debatable..(ORF, promoter, pseudogene, gene product, etc)
1 gene = how many proteins? (never known)
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Why Proteomics?
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Differential protein expression
Scenario 1: can be analyzed by microarray technology
DNA RNA Protein
Transcription Translation
x1 x4
DNA RNA Protein
Transcription Translation
x3
Stimulus
DNA RNA Protein
Transcription Translation
x3
Stimulus
Scenario 2: can be solved by proteomics technology
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What proteomics can answer
Protein identification Protein Expression Studies Protein Function Protein Post-Translational Modification Protein Localization and Compartmentalization Protein-Protein Interactions
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General classification for Proteomics
Protein Expression comparison (beginning) Quantitative study of protein expression between
samples that differ by some variable Structural Proteomics (simulation)
Goal is to map out the 3-D structure of proteins and protein complexes
Functional Proteomics (everything) To study protein-protein interaction, 3-D structures,
cellular localization and PTMS in order to understand the physiological function of the whole set of proteome.