BBMB 405 1st Edition Lecture 41Outline of Last Lecture XVIII. Chapter 33: Sensory SystemsD. Hearing depends on the speedy detection of mechanical stimuliE. Photoreceptor molecules in the eye detect visible lightXIX. Chapter 35: Molecular MotorsA. IntroductionOutline of Current Lecture XIX. Chapter 35: Molecular MotorsB. Most Molecular-Motor Proteins are members of the P-loop NTPase superfamilyC. MyosinsMove along actin filamentsD. Kinesin and dynein move along microtubulesCurrent LectureXIX. Chapter 35: Molecular MotorsB. Most Molecular-Motor Proteins are members of the P-loop NTPase superfamily1. Cytoskeletal motor proteins utilize a “track”a. Cytoskeletal fivers are tracks: actin filaments, microtubulesb. Myosin molecules form a thick filament at the center of actin filaments2. Three major families of eukaryotic motor proteinsa. Myosin- Move along actin filaments- Less than 40 distinct myosins in humans- Muscle contractions, cell division, organeller movementb. Kinesin- Move along microtubules- Less than 40 distinct human kinesins- Protein, mRNa, and vesicle transport, chromosome segregationc. DyneinThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Move along microtubules- About 10 distinct dyneins in humans- Motion of cilia and flagella, vesicle transport, transport during mitosis3. Myosin dissectiona. Four fragments are generated by treatment of myosin with proteasesb.c. S1 is the head; light meromyosin is a coiled coil, mero – “part of”d. Light chains wrap around alpha-helix of head domain4. Motor proteins are powered by ATP hydrolysisa. P-loop: phosphate binding; P-loop NTPase aka Walker A motifb. Myosin and kinesin both contain P-loop NTPase domains, structural similarities dispite lack of sequence similarity5. Motor proteins are powered by ATP hydrolysisa. Dynein motor domain is much larger than kinesin motor domainb. Contains six AAA ATPase domainsc. Subfamily of the P-loop NTPased.e.6. The tracksC. MyosinsMove along actin filaments1. The tracksa. Actin filaments: Globular (G)-Actinb. Microtubules: Minus end is toward cell center and plus end is toward cell surfacec. Polar: directionalityd. Dynamic: assemble and disassemble based on subunit concentration and/or nucleotide statee. Filamentous actin (F-actin)-tropomyosin2. Dynamics of F-actin are based on critical concentration of G-actina. Critical concentration (CC): concentration at which actin polymerizesb. See figure in sides3. ATP binding and hydrolysis is coupled to motor protein movement and track binding; transition state analog for ATP hydrolysis; post ATP-hydrolysis and release of Pi (power stroke, 90 degree rotation of lever arm; switch loops tightly conform to gamma-phosphoryl and relax when group is absent4. Myosin moving along actin; error in figure: yellow arm should be switched in drawing between steps 4 and 55. Kinesin and dynein a. Single D. Kinesin and Dynein move along microtubules1. Kinesin and dynein are processive and travel in specific directiona. Single TMR-labeled dynein molecules can be seen moving processively along axonemal microtubulesb.2. The relay helix and neck linker contribute to kinesin movementa. Neck linker is flexibleb. Nucleotide exchange occurs upon association of head domain/ADP complex with microtubulec. Neck linker conforms along head domain, increasing affinity for microtubuled. Conformational change repositions other head domaine. ATP is hydrolyzed upon head domain interaction with microtubule3. Kinesin moving along microtubule: processive, hand-over-hand
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