Beruflich Dokumente
Kultur Dokumente
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Paramecium beating cilia
And
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Prof. Ben Feringa, University of Groningen,
Nobel Prize in Chemistry, 2016
“Go beyond our current horizon”
At IIT-Delhi
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Motor Proteins
• All motor proteins transduce chemical energy from nucleotide
hydrolysis to movement.
• Motors are encoded by multigene families.
• Individual gene is highly conserved in organisms as diverse as
yeast to human.
• Motors , structurally divided into two domains: a head which
contains the motor and a tail which interacts with its cargo.
• Head domain: highly conserved within members of a super family;
Tails: highly divergent.
• In multi-subunit complexes, a single type of motor could be used in
several different machines by virtue of its association with
functionally diverse tails.
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Types of molecular motor proteins
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MICROTUBULES: The Tubulins
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Actin
• Monomeric subunit of microfilaments
• Highly conserved through evolution
• Binds to ATP or ADP
• Two forms:
– G-actin: globular monomeric actin
– F-actin: filamentous polymeric actin; called Thin Filament.
Polymerization
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Polymerization
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Myosin
• Contractile force of muscle generated by the interaction of two
proteins, myosin and actin.
• Together, actin and myosin make up more than 80% of the protein
mass of muscle.
• Molecules of myosin aggregate to form structures called thick
filaments. (F-actin: filamentous polymeric actin; called thin
filament)
• The thick and thin filaments that undergo transient interactions
and slide pass each other to bring about contraction.
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Myosin structure
• Two heavy chains, two essential light chains, and two regulatory
light chains
• Heavy chain has head domain, neck region, and tail domain.
• Head domain contains actin-binding site and ATP-binding site
• Tail domain is a dimeric coiled-coil
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Myosin
• Skeletal muscle consists of parallel bundles of muscle fibers, each
fiber a single, very large, multinucleated cell, (20 to 100 µm in
diameter), formed from many cells fused together. Each fiber
contains about 1,000 myofibrils, (2 µm in diameter), each
consisting of a vast number of regularly arrayed thick and thin
filaments complexed to other proteins.
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Cross bridge cycle
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Kinesin
• Within cells, proteins, organelles, and vesicles move many micrometers along well-
defined routes in the cytosol and delivered to particular addresses.
• In Nerve cells microtubules function as tracks in the intracellular transport of various
types of “cargo.”
• To date, approximately 10 different kinesin subfamilies identified. All contain a globular
head (motor) domain, but differ in their tail domains and several other properties.
• Two broad functional groups— cytosolic and mitotic kinesins.
Cytosolic kinesins: vesicle and organelle transport.
Mitotic kinesins: spindle assembly and chromosome segregation in cell
division.
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Kinesin moves in 8 nm steps corresponding to the distance between successive alpha- and
beta-Tubulin monomers in a protofilament. Moves from –ve to +ve direction of
microtubules.
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Molecular Cell Biology. 5th Edition. 2004.
Kinesin delivering cargo in brain through neuron
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Dynein
• A microtubule-based molecular motor involved in axonal transport, mitosis, and
cilia/flagella movement.
• Two types: Cytoplasmic and Axonemal
• Unlike kinesin and myosin dynein form large molecular complexes. E.g.,: one
axonemal dynein molecule of Clamidomonous composed of three dynein heavy
chains, two intermediate chains, and more than ten light chains.
• Cargoes: lysosomes, endosomes, phagosomes, golgi complex.
• Dynein mediates transport to the (-) end of MTs (opposite to Kinesin)
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• Dynein present in cilia and flagella are termed axonemal dyneins.
• Cilia and flagella: found on a variety of cell types, from single cell protozoa and
“sperm” to the ciliated surface of respiratory and reproductive tracts.
• Ciliary motility is generated by the dynein-driven sliding of doublet
microtubules.
• Defects in the dynein motors or components that regulate their activity can have
profound consequences; in vertebrates, these include infertility, respiratory
disease, and defects in the determination of the left–right axis during
embryonic development. These defects are called “Ciliopathies”.
• No medicine.
And
100 fps
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Video 1: Bacterial Infection and microtubule
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References
• Lehninger Principles of Biochemistry. 5th Edition. 2008. David L. Nelson and
Michael M. Cox.
• Molecular Cell Biology. 5th Edition. 2004. Lodish, Berk, Matsudaira, Kaiser,
Krieger, Scott,Zipursky and Darnell.
• Alberts B and Lye RM (1992) Unscrambling the puzzle of biological machines:
The importance of the details. Cell 68:415-420.
• Howard J (1997) Molecular motors: Structural adaptations to cellular functions.
Nature 389:561-567.
• Kikkawa M (2013) Big steps toward understanding dynein. J Cell Biol 202:15-23.
• Porter ME and Sale WS (2000) The 9+2 axoneme anchor multiple inner arm
dyneins and a network of kinases and phosphatases that control motility. J Cell Biol
151: F37-42.
• Sowa Y and Berry RM (2008) Bacterial flagellar motor. Quarterly Rev Biophy
41:103-132.
• Vallee RB, Williams JC, Varma D, Barnhart LE (2004) Dynein: An ancient motor
protein involved in multiple modes of transport. J Neurobiol 58:189–200.
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Videos
• https://www.youtube.com/watch?v=Ct8AbZn_A8A
• https://www.youtube.com/watch?v=y‐uuk4Pr2i8
• https://www.youtube.com/watch?v=tMKlPDBRJ1E
• https://www.youtube.com/watch?v=BbI47l2nbDQ
• https://www.youtube.com/watch?v=mu72Qoy1xq0
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