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Motor Proteins - Introduction Part 1 Biochemistry 4000 Dr. Ute Kothe.

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Presentation on theme: "Motor Proteins - Introduction Part 1 Biochemistry 4000 Dr. Ute Kothe."— Presentation transcript:

1 Motor Proteins - Introduction Part 1 Biochemistry 4000 Dr. Ute Kothe

2 Motor Proteins Motor Proteins convert chemical energy into motion. chemical energy is derived from ATP hydrolysis motion is generated by conformational changes depending on the bound nucleotide MyosinKinesin Dynein

3 Motor Protein Function Myosin (18 known classes, 40 different myosins in humans)  Movement along actin fibres Muscle movement Cytokinesis (cytoplasmic division, tightening of contractile ring) Transport of cargo along microfilaments (vescicles etc.) Kinesin (16 classes)  Movement along microtubule tracks, usually to (+) end Transport of cargos: vesicles, organelles, cytosolic components such as mRNAs & proteins, chromosomes Dynein (12 mammalian dyneins)  Movement along microtubule tracks, to (-) end, i.e. cell center Cytoplasmic dyneins: transport of cargos such as vesicles Axonemal dyneins: Movement of cilia and flagella

4 Tubulin Voet Fig. 35-89 Tubulin  + GTP Tubulin  + GDP building block of microtubules heterodimer of closely related Tubulin  &  G proteins: N-terminal residues fold into G domain-like structure  -tubulin’s GTP buried at subunit interface, nonexchangable, not hydrolyzed  -tubulin’s GTP is solvent exposed until tubulin dimers polymerize upon polymerization,  -tubulin from adjacent dimer provides catalytic residue to hydrolyze b-tubulin’s GTP; resulting GDP is nonexchangeable unless tubulin dissociates from microtubule

5 Microtubules Voet Fig. 35-92 1.Tubulins interact head to tail to form a long protofilament 2.Protofilaments align side by side in curved sheet 3.Sheet of 13 (9-16) protomers closes on itself to form microtubule 4.Microtubule lengthens by addition of tubulins to both ends (preferentially to + end, i.e. the end terminating in  -tubulins)

6 Structure of the Axoneme Voet Fig. 35-102 Bundle of microtubules called axoneme coated by plasma membrane Forms eukaroytic flagella & cilia

7 Dynein Valle, Cell 2003; Voet Fig. 35-107 1 or more heavy chains (motor domain) several intermediate and light chains motor domain is 7-membered ring, ATP- hydrolyzing unit coiled-coil extension forms stalk that interacts via globular domain with microtubules long stem (with intermediate and light chains) binds cargo

8 Conventional Kinesin Voet Fig. 35-94 two identical heavy chains forming two large globular heads attaching to microtubules and a coiled-coil two identical light chains interacting wit cargo transports vesicles and organelles in (-) to (+) direction (towards cell periphery)

9 Kinesin Structure Voet Fig. 35-95 & 96 & 97 Globular head: tubulin-binding site & nucleotide binding site flexible neck linker  -helical stalk leading into coiled-coil ATP hydrolysis triggers conformational change in neck linker via 2 switch regions: When ATP is bound, neck linker docks with catalytic core Upon ATP hydrolysis, the neck linker “unzips”

10 Voet Fig. 35-98 Kinesin Cycle

11 Hand-over-Hand Mechanism ATP-bound state: strong microtuble binding ADP-bound state: weak microtubule binding 1.ATP binds to leading head - globular kinesin head which is already bound to the microtubule and oriented towards (+) end 2.Neck linker of leading head “zips up” agains catalytic core 3.trailing head is thrown forward (trailing head has bound ADP and reduced affinity to microtubule): 4.Trailing head swings by ~ 160 Å, net movement of dimeric kinesin is ~ 80 Å = length of one microtubule dimer 5.ATP in new trailing head is hydrolyzed & phosphate released: affinity for microtuble decreases 6.ADP in new leading head dissociates  Two heads work in a coordinated fashion  ATP binding to leading head induces power stroke

12 Processivity Kinesin is highly processive: it takes several 100 steps on a microtubule without detaching or sliding backwards! How? coordinated, but out of phase ATP cycle in both heads one head is always firmly attached to microtubule Movie demonstrating kinesins processivity: http://www.proweb.org/kinesin/axonemeMTs.html

13 Dynein Valle, Cell 2003; Voet Fig. 35-107 1 or more heavy chains (motor domain) several intermediate and light chains motor domain is 7-membered ring, ATP- hydrolyzing unit coiled-coil extension forms stalk that interacts via globular domain with microtubules long stem (with intermediate and light chains) binds cargo


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