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Transcript
‫بخش مهندسی بیوتکنولوژی‬
‫عنوان درس‪:‬‬
‫زیست شناسی سلولی و مولکولی ( ‪Cellular and Molecular‬‬
‫‪)Biology‬‬
‫تعداد واحد‪( 2 :‬نظری)‬
‫روش ارزیابی‪:‬‬
‫‪ %15‬سمینار‪ %35 ،‬میان ترم و ‪ %50‬پایان ترم‬
Scientific Journals
• Cell
• Science
• Nature
• Nature Reviews Molecular Cell Biology
• Nature Reviews Genetics
• Annual Review of Genetics
‫سر فصل مطالب‬
‫• تعریف بیولوژی‪ ،‬مشخصات سلولی‪ ،‬بیولوژی سلولی و شاخه های‬
‫آن‪ ،‬ویژگیهای موجودات مدل در مطالعات سلولی‪ ،‬پروتئین ها‬
‫به عنوان مولکولهای فعال سلولی‪ ،‬قابلیت دسترسی بیولوژیکی‬
‫به پروتئین ها‪ ،‬اندامک های دخیل در سنتز‪ ،‬تاخوردگی‪ ،‬تغیر‬
‫و تخریب پروتئین ها‪ .‬نقش گلیکوزیالسیون در سلول‪ ،‬برهمکنش‬
‫پروتئین و قند‪ ،‬غشاهای سلولی و بررسی اجزای آن‪ ،‬انواع‬
‫پروتئین های غشایی‪ ،‬تنظیم فعالیت های سلولی به کمک سیگنال‬
‫های غشا و اجزای آن‪ ،‬برهمکنش پروتئین چربی و قند در سلول‪،‬‬
‫ساختار سلول گیاهی و اندامک ها‪ ،‬غشای سلولی و انتقال‬
‫منابع‬
• Bruce, Alberts, et al. Essential cell biology. Garland Science.
• Gerald, Karp. Cell and Molecular Biology: Concepts and
Experiments. John Wiley & Sons.
• Harvey, Lodish, et al. Molecular cell biology.
The origins of the universe
• Cosmologists believe that the universe
was born 14 billion years ago in the Big
Bang
Origin-of-life conundrum
• The crash of meteors on early Earth likely generated hydrogen
cyanide, which could have kick-started the production of biomolecules
needed to make the first cells.
Chicken-and-egg problem!
• Central dogma
• Alkaline formose reaction
• Miller-Urey spark discharge experiment
• Oro’s experiments
The origin of life probably occurred in three
overlapping phases
The RNA world hypothesis
• Store information
• Self replicate
• Self-cleavage
• Cleavage of other RNAs (RNase P)
• Catalyze reactions (ribozymes)
RNA
Or
PNA
Or
TNA
Evolution of life
First evidence for eukaryotic cells—
structures resembling single-celled
algae—about 1.4 billion years ago and
for multicellular algae about 0.9 billion
years ago.
Aspects of biological science
• Astrobiology
• Biochemistry
• Botany
• Biophysics
• Cell biology
• Computational biology
• Ecology
• Evolutionary biology
• Genetics
• Marine biology
• Microbiology
• Molecular biology
• Paleobiology
• Physiology
• Structural biology
• Systems biology
• Synthetic biology
• Zoology
‫بیوسفر‬
‫اکوسیستم‬
‫موجودات زنده‬
‫اندام‬
‫بافت‬
‫سلول‬
‫اندامک‬
‫ها‬
‫مولکول‬
The Two Empires and Three Domains of Life
What Defines a Cell?
What Other Components Do Cells Have?
Figure 2: The composition of a bacterial cell
Most of a cell is water (70%). The remaining
30% contains varying proportions of structural
and functional molecules
How Did Cells Originate?
Figure 5: The origin of mitochondria and chloroplasts
Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that
once lived as independent organisms. At some point, a eukaryotic cell
engulfed an aerobic prokaryote, which then formed an endosymbiotic
relationship with the host eukaryote, gradually developing into a
mitochondrion. Eukaryotic cells containing mitochondria then engulfed
photosynthetic prokaryotes, which evolved to become specialized chloroplast
organelles.
Two competing evolutionary scenarios for the origin of eukaryotic
cells and their mitochondria.
(A) The traditional view posits that the bulk of eukaryotic cellular
complexity arose in a stepwise fashion prior to the endosymbiotic
uptake (by phagocytosis) of the a-proteobacterium that became the
mitochondrion.
(B) The hydrogen hypothesis invokes a metabolic symbiosis
between methane-producing archaea and a-proteobacteria. In this
scenario eukaryotic cellular complexity arises after endosymbiosis.
Both models involve extensive gene transfer from
the a-proteobacterium to the archaeal host and the evolution of a
system for targeting nucleus encoded proteins to the
endosymbiont-turned organelle.
Earth’s biogeologic clock
Model organisms
• All cells are thought to be descended from a common ancestor, whose
fundamental properties have been conserved through evolution. Thus,
knowledge gained from the study of one organism contributes to our
understanding of others, including ourselves.
• Short generation time
• Characterized genome
• Similarity to humans
• Extensively studied in research laboratories
• Small, easy and cheap to maintain and manipulate
• Fewer ethical concerns
Current models
• Viruses
Phage lambda
SV40
Tobacco mosaic virus
Herpes simplex virus
• Prokaryotes
• Escherichia coli
• Bacillus subtilis
Current models
• Eukaryotes
Caenorhabditis elegans
Drosophila melanogaster
Mus musculus
Xenopus
Zebrafish
HeLa cell
Current models
• Eukaryotes
Chlamydomonas reinhardtii
Neurospora crassa
Saccharomyces cerevisiae
Arabidopsis thaliana
Brachypodium distachyon
Tobacco BY-2 cells
Rice
Populus
‫جلسه دوم‬
proteins
• Proteins are biomacromolecules present in all organisms and they have
a large variety of functions.
• Proteins are linear chains of L-α-amino acids .
• Structural: offering stiffness and rigidity to fluid biological components. Collagen is the
most abundant structural protein in mammals or Scafold proteins.
• Catalysis of chemical reactions as enzymes. Only a small region of an enzyme called the
active site binds the substrate and contains the catalytic residues.
• Receptors: they usually have a ligand-binding site on the cell surface and an effector
domain within the cell, which may have enzymatic activity or may undergo a
conformational change.
• Signaling proteins:
• Channels for molecules to pass through the cell membrane, for example the potassium
channel.
• Transport: Those proteins bind small molecules and transport them to other locations in
the cell or organism. For example haemoglobin transports oxygen.
• Motor proteins: responsible for moving other proteins, organelles, cells even whole
organisms.
Molecular machine
• most functions in the cell are not carried out by single protein
enzymes, but by macromolecular complexes containing multiple
subunits with specific functions.
• Many of these complexes are described as “molecular machines.”
Replisome, Spliceosome, and ribosome
Proteome
• A proteome is the entire set of proteins expressed by a genome, cell,
tissue, or organism at a certain time.
• Structural proteomics
• Expressional or Analytical Proteomics
• Functional or Interaction Proteomics
Hierarchical Structure of Proteins
• A key concept in understanding how proteins work is that function
is derived from three-dimensional structure, and three dimensional
structure is determined by both a protein's amino acid sequence and
intramolecular noncovalent interactions.
Hierarchical Structure of Proteins
• The Primary Structure of a Protein Is Its linear Arrangement of
Amino Acids
-Aia-Giu-Val-Thr-Asp-Pro-Giy-
Hierarchical Structure of Proteins
• Secondary Structures Are the Core Elements of Protein
Architecture
• alpha Helix
• Beta Sheet
• Beta Turn
• irregular structure
• Random coil
‫‪alpha Helix‬‬
‫• در مارپیچ آلفا اسکلت مولکول به شکل مترپیچ می باشد که در آن اتم اکسیژن کربونیل از‬
‫هر پیوند پپتیدی با اتم هیدروژن آمید ‪ 4‬اسید آمینه جلوتر پیوند هیدروژنی تشکیل می دهد‪.‬‬
Coiled coil
Beta Sheet
‫‪Beta turn‬‬
‫• از ‪ 4‬اسید آمینه تشکیل شده اند‪.‬‬
‫• تا خوردن پلی پپتیدهای بلند را تسهیل میکنند‬
‫• گلیسین و پرولین رایج ترین اسیدهای آمینه در این‬
‫ساختار می باشند‪.‬‬
Tertiary Structure Is the Overall Folding
of a Polypeptide Chain
• Tertiary structure refers to the overall conformation of a polypeptide
chain-that is, the three-dimensional arrangement of all its amino acid
residues.
Quaternary Structure
• Many proteins are made up of multiple polypeptide chains, often
referred to as protein subunits.
• The quaternary structure refers to how these protein subunits interact
with each other and arrange themselves to form a larger aggregate
protein complex.
• hydrogen-bonding, disulfide-bridges and salt bridges affect stability of
protein complex.
• Proteins usually fall into one of three broad structural categories,
based on their tertiary structure
• Globular proteins
• Fibrous proteins
• Integral membrane proteins
Structural Motifs
• A particular combination of two or more secondary structures
that form a distinct three-dimensional structure.
Domain
• Distinct regions of protein structure often are referred to as domains.
• Functional
• Structural
• Topological
Protein Folding
• In thermodynamic terms, the native state is usually the conformation
with the lowest free energy (G)
• What features of proteins limit their folding from very many potential
conformations to just one?
Folding of Proteins in Vivo
• Molecular chaperones: HSP70, Bip,Dnak
• Chaperonins: GroEL/GroES,TriC
Protein function
• The molecule to which a protein binds is called its ligand.
• Specificity
• Affinty
• Molecular complementarity
Regulating Protein Function
• Increase or decrease the steady-state level of the protein
• Change the intrinsic activity
• Change in location or concentration with in the cell of the protein
itself, the target of the protein's activity (e.g., an enzyme's substrate),
or some other molecule required for the protein's activity (e.g., an
enzyme's cofactor).
Regulated Synthesis and Degradation
of Proteins
• The life span of intracellular proteins varies from as short as a few
minutes to as long as the age of an organism.
• One major pathway is degradation by enzymes within lysosomes
(autophagy)
Proteasome
• Proteasomes are very large, protein-degrading macromolecular
machines