Molecular Motors

basic mechanism of motor proteins

they covert the chemical energy by utilizing ATP and causing allosteric conformational changes which makes kinetic energy for movement of motor proteins

what do molecular motors do?

transfrom chemical energy (ATP) to kinetic energy

where do motor proteins work?

on the cytoskeleton

composition of actin

2 copies of heavy chains, essential light chains and regulatory chains

2-headed structure linked with coiled-coil stalk with ATPase activity on the domain head

what does Myosin work on/move along?

actin

what do kinesins work on?

microtubules

what do dyenins work on?

microtubules

what do dyneins power?

cilia and flagella movement

what direction does Myosin work in?

the + direction

what direction do kinesins travel?

the + end

what direction do dyenins travel?

towards the - end

how many types of kinesins are there?

40

how many types of dyenins are there?

10

what is the function of class 1 myosin?

moves membrane around actin

what is the function of class II myosin?

it forms thick filaments in the muslce

what is the function of class V myosin?

moves actin around its filaments

what molecule can cleave the head of myosin II?

papain

what is the function of the head of myosin?

it has the motor activity

where is ATP hydrolized on myosin?

in the head

what is the structure of the myosin tail?

coil-coil alpha helices

where is the actin binding site on myosin?

in the head

what structure makes up the actin binding site?

a p-loop

what is the function of myosin 2 regulatory chains?

they stiffen the neck region

what is the function of the head domains in kinesins and dyneins?

to allow them to walk along the microtubule

what is the function of the light chains in kinesin and dyenin?

to bind the motors to their cargo

how was the structure of myosin discovered?

using X-ray crystalography

what triggers the cocking phase of myosin?

the binding of ATP

what triggers the power stroke of myosin?

the hydrolosis of ATP to ADP

when does myosin bind to actin?

during the power stroke

what is the rigor conformation?

when myosin is bound to actin in the absense of ATP

processivity

the proportion of the cycle of the motor that is in contact with the substrate

what fragments of myosin control proteolysis

S1, S2, heavy meromyosin (HMM) and light meromyosin (LMM).

what does s1 bind of myosin bind?

α helix component of S1 binds the essential and regulatory light chains

Conventional kinesin

dimer with two-head domains linked to a long coiled-coil.

At the opposite end from the head domains are cargo-binding domains, which also bind to light chains.

Dynein composition

member of the AAA subfamily of ATPases, has a head domain composed of six P-loop NTPase domains

what was the 1st motor protein identified

Myosin 2

how to digest light meromyosin

trypsin

essential light chain cofactor myosin

ca2+

regulatory light chain cofactor

mg2+

calmodulin in myosin

can bind an alpha helix by wrapping around it like essential light chain and regulatory lights

myosin structure

coiled coiled structure

2 alpha helices

bound by hydrophobic residues

role of myosin 1

bind membrane and exert force ie endocytosis

role of myosin 2

Bouquet of molecules acting on actin filament (muscle) ie contraction

role of myosin 5

intercellular transport

kinesin structure

head domain

neck linker

coiled coil

light chains

S1 fragment of myosin vs kinesin:

Myosin:

• motor activity is by s1

• s1= lever arm, nucleotide binding site with switch (rotation after atp bound)

kinesin

• does the conformation change with atp

• lever arm in myosin= neck linker ie transmit and convert chem to kinetic

Actin Monomer Structure

four domains that surround a nucleotide-binding site

Actin Filament Formation

Actin monomers polymerize to form actin filaments, also known as F-actin (Filamentous Actin). These filaments have a two-stranded helical structure resembling a cable.

actin polarity

barbed (Plus) End and Pointed (Minus) End

Arp2/3 Complex, purpose

is a protein complex that plays a crucial role in assisting the formation of actin filaments. It promotes the branching of actin filaments, contributing to the organization and dynamics of the actin cytoskeleton.

promotes the initial unfavorable interaction of g-actin

decorated actin

Myosin S1 binds to actin in the absence of ATP

The conformation of the myosin head domain changes in the presence of actin to increase the interaction with the actin filament

purpose of optical trap

observing Single myosin molecules moving along an actin filament.

Individual myosin heads bind the filament and undergo a conformational change called the power stroke that pulls the actin filament

myosin ATPase cycle

• myosin binds ATP at s1

• ATP hydrolysis to ADP and Pi. This catalyzed by ATPase

• myosin disassociation: this causes a conformational change in the head and weakens affinity

• power stroke: Pi is released and myosin moves back onto the filament

• ADP release: ready to repeat cycle