Download - Cytoskeletal Protein - Microtubule
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Cytoskeleton Protein - Microtubule
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Eukaryotic cell Skeletal SystemThree well defined filamentous structures
Micotubules
Microfilaments
Intermediate filaments
Cytoskeleton
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Eukaryotic cell Skeletal System
Micotubules
Rigid tubes
Tubulin
Microfilaments
Solid / thinner
Actin
Intermediate filamentsTough ropelike fibres
Many related proteins
Cytoskeleton
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Functions of Cytoskeleton
1 Dynamic scaffold
2 Internal framework
3 Network of highways
4 Cell movement
5 m-RNA anchoring
6 Cell division
Cytoskeleton
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MicrotubulesStructure and Composition
Components of a diverse array of structures
Mitotic spindle
Core of flagella and cilia
Tubes of globular proteins
Longitudinal rows
Protofilaments
Cross-section13 rows of protofilamentscircular
Dimeric building blocksa-tubulin and b-tubulin
Cytoskeleton
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MicrotubulesStructure and Composition
a-tubulin and b-tubulin
Similar 3-D structure
Form dimers
Fit togethernon-covalent bonds
Cytoskeleton
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MicrotubulesStructure and Composition
a-tubulin and b-tubulin
Linear array
Asymmetric
a-tubulin at one end
b-tubulin at other endSame polarity
Plus end = fast growing
Minus end = slow growing
Cytoskeleton
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MicrotubulesStructure and Composition
a-tubulin
Bound GTP
Not hydrolysed
Non-exchangable
b-tubulin
Bound GDP
Exchanged for GTP prior to assembly
Cytoskeleton
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Microtubule Associate Proteins (MAPs)
Mostly in brain
ExceptionMAP4many cell types (non-neuronal)
Domain attaches to microtubule
Domain extends outfilament
Various roles
Cross-bridges connecting microtubules
Increase microtubule stability
Alter microtubule rigidity
Alter microtubule rate of assemblyActivityphosphatases and phosphokinases
Cytoskeleton
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Microtubulesstructural roles
Determine cell shape
Axons of nerve cells
Internal organization
Axonal transportationMaterials moved from cell bodyalong axon
Anteriograde
From axon to cell bodyendocytosis
Retrograde
Axons have microfilaments, intermediate filamentsand microtubules
Interconnected
Cytoskeleton
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Microtubulesstructural roles
Passive
Tracks for many motor proteins
Motor proteins use ATP
Move cellular cargo
Vesicles, Mitochondria, Lysosomes, Chromosomes
Motor proteinsThree families
Myosins
Kinesins
Dyneins
Kinesins and Dyneinsmove on microtubules
Cytoskeleton
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Motor proteins
Move unidirectionally
Stepwise
Series of conformational changes
A mechanical cycle
Coupled to chemical cycleEnergy
Steps
ATP binding to motor
Hydrolysis of ATP
Release of ADP and Pi
Binding of new ATP
Cytoskeleton
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Motor proteins
KinesinTetramer
2 identical heavy and 2 identical light chains
Functional domains
Pair of globular heads
Bind microtubule
ATP-hydrolysing
Neck / stem and tail
Tail binds cargo
Move toward plus end of microtubule
Plus end directed
Cytoskeleton
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Motor proteins
Kinesin
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Motor proteins
KinesinVelocity proportional to [ATP]
Move one heterodimer at a time (step)
One headalways attached
Heads are coordinated
Each at different stages of chemical and mechanical cycles
When one head binds
Conformational change in adjacent neck region
Swings other head forward
Kinesinwalks along microtubule
Cytoskeleton
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Motor proteins
KinesinOne member of a superfamily of related proteins
Kinesin related proteinsKRPs
Kinesin-like proteinsKLPs
> 50
Heads similar
Tails heterogenousbinding different cargoes
Cytoskeleton
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Motor proteins
Kinesin-mediated organelle transportKinesins aligned with plus ends away from nucleus
Tend to move organelles in anterograde direction
Cytoskeleton
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Motor proteins
Cytoplasmic DyneinMovement of cilia and flagella
And ubiquitous motor protein in eukaryotic cells
Huge - > 1.5 Mda
2 identical heavy chainsMany intermediate and light chains
Heavy chain
Large globular head
Force generating engine
Minus end directed
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Motor proteins
Cytoplasmic DyneinTwo rolesForce generationspindlemitosis
Minus-end directed motor for Golgi Complex and vesicles
Requires a sub-unit complex dynactin
Cytoskeleton