Pages 1010-1034

Molecular Motors

General Characteristics of Molecular Motors

Motor proteins – bind to a polarized cytoskeletal filament and use the energy derived from repeated cycles of ATP hydrolysis to more steadily along it

-They differ in the type of filament they bind to, the direction in which they move along the filament, and the “cargo” they carry.

Myosin II Structure

Myosin was the first motor protein identified and is responsible for muscle contraction. It is formed from 2 heavy chains and 2 light chains.

Myosin II Thick Filament

Motor Activity is Located in the Myosin Head

Myosin Superfamily Tree

-Myosin tails have diversified during evolution to permit the proteins to dimerize with other subunits and to interact with different proteins or cargo. Humans have about 40 myosin genes

Kinesin

Kinesin is a motor protein that moves along microtubules

It was first identified is the giant axon of the squid, where it functions to carry organelles away from the neuronal cell body toward the axon terminal by walking toward the + end of microtubules

Many kinesins or kinesin-related proteins function in organelle movement or have specific roles in mitotic and meiotic spindle formation and chromosome separation.

Kinestin and Kinestin-Related Proteins

Goes towards + endGoes towards – endIncreases dynamic instabilityMonomer

Dynein Structure

Dyneins are a family of – end directed microtubules motors- are the largest and fastest molecular motors

Cytoplasmic dynein - important for vessicle trafficking and localization of the Golgi apparatus

Ciliary dynein - important in the beating of cilia and flagella

Myosin and Kinesin Structure

-They have nearly identical cores

Myosin Walking Cycle

Attached

Released

Cocked

Force-Generating

Attached

Rigor state

Comparison of Kinesin and Myosin

Motor Proteins are Adapted to Cell Functions

Kinesin –moves in a highly processive fashion, traveling hundred of ATPase cycles on a microtubule before dissociating

Myosin II – makes just one or a few steps along an actin filament before dissociating

Two Reasons:1. the cycles of the two motor heads in a kinesin dimer are coordinated with each other, so that one kinesin head does not let go until the other is ready to bind2. kinesin spends a larger fraction of its ATPase cycle tightly bound to the microtubule

Walking Direction of Kinesin Family Proteins

The coiled-coil domain seems to determine the directionality of movement

Attachment Model of Dynein to an Organelle

Motor proteins also have a significant role in organelle transport along actin filaments

Effect of Microtubule Depolymerization on the Golgi Apparatus

Green – Golgi apparatusRed – microtubules

Golgi are being positioned near the center of the cell by dyneins moving towards the – end of microtubules

Myosin V on Melanosomes

Black – melanosomesGreen – Myosin V

Melanosome Movements in Fish Pigmented Cells

-Both dynein and kinesin are associated with pigment granules

Regulation of Myosin II

Non-muscle myosin

Skeletal Muscle Cells

Skeletal Muscle Myofibrils

Longitudinal section

The Sarcomere

Sliding-Filament Model for Muscle Contration

Accessory Proteins in a Sarcomere

Alpha-actinin

Calcium Release in the Sarcoplasmic Reticulum

Regulation of Skeletal Muscle Contraction

TroponinT=tropomyosin bindingI=InhibitoryC=Ca++ binding

Resting stateI,T pulls tropomyosin out of its normal binding groove and blocks myosin

Active stateC binds Ca++ and releases tropomysoin allow the interaction of actin and myosin

Effect of Subtle Mutations in Cardiac Myosin

6-day old mouse

Flagella and Cilia Movements

Microtubules in a Flagellum or Cilium

Cilliary Dynein

Bending of an Axoneme

Structure of Basal Bodies

Kartagener’s syndrome – defect in ciliary dynein

Base of cilia and flagella, and centrioles