Molecular Molecular motorsmotors

Molecular MotorMolecular MotorDefinitions & Introduction :-Molecular motor, protein or protein complex that transforms chemical energy into mechanical work at a molecular scale. The chemical process that produces energy is hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) & phosphate.Rotatory & translatary motors are known to exit.Motor proteins move in eukaryotic cells along filaments (actin filaments, microtubules) periodic and relatively rigid protein structures with a periodicity of the order of 10 nanometers. Some of the known motors are myosin that moves along actin filaments and kinesin and dynein that move along microtubules. They play a role in => muscular contraction => cell division => cellular material transport etc.

ExamplesSome examples of biologically important molecular motors.=>Motor proteins:- Myosin is responsible for muscle contraction. Kinesin moves cargo inside cell away from the muscle along microtubules. Dynein produces the axonamal beating cilia and flagella and also transport cargo along microtubules towards the cell nucleus. Nanobot is a newer biologically important molecular motor.=>Fo F1 ATP Synthase generates ATP using the transmembrane electrochemical proton gradient inside the mitochondria.=>RNA Polymerase transcribes RNA from DNA.=>Actin polymerization generates forces and can be used for propulsion.=>Synthetic molecular motors have been created by chemist that yield rotation, possibly generating torque.

Kinesin:- it is a the name given to a class of motor proteins found in biological cells.

Function:-In the cell, small molecular such as gases and glucose diffuse to where they are needed. Large molecules synthesized in the cell body, intracellular components such as vesicles, and organelles such as mitochondria are too large (and cytosole too crowded) to diffuse to their destinations. Most kinesin transport such cargo about the cell by making unidirectional along microtubule tracks, hydrolyzing one molecule of ATP at each step. It was thought that ATP hydrolysis powered the kinesin walk but it now seems that the force of binding to the microtubules is what pull the cargo along while the binding of ATP assists the direction of motion.

Structure:- The typical kinesin is a protein dimer consisting of two heavy chain and two light chain. The heavy chain comprises a globular head (motor domains) connected via a short, flexible neck liker to the stalk along, central coiled region that ends in a tell region from with a light chain. The stalk intertwine to form the kinesin dimer. Cargo binds to the tail while the twin heads alternately bind the microtubules the kinesin pulls the cargo along.Polarity:- Motor proteins travels in a specific direction along a microtubule. This is because the microtubule is polar, the head only bind to the microtubules in one orientation and ATP hydrolysis drives the molecules in one direction.Most kinesin walk towards the plus end of microtubules which in most cells entails the transporting cargo from the center of the cell towards the periphery. This form of transport is known as anterograde transport. Some kinesin and a different type of motor protein known as dyneins move towards the minus end of microtubules. Thus they transport cargo from the periphery of the cell towards the center, this is known as retrograde transport.

KinesinKinesin

Proposed mechanisms :-Kinesin accomplishes transport by essentially “walking” along a microtubule. Two mechanism have been proposed to explain how this movement occurs. In “hand over hand” mechanisms, the kinesin heads step over one other alternating the lead position. In the “inchworm” mechanisms, one kinesin head always leads, moving forwards a step before a the trailing head catches up.

Dynein :- Dynein is a motor protein (also called molecular motor) in cells which convert the chemical energy contain in ATP into the mechanical energy of the movement. Dynein transport various cellular cargo by walking along cytoskeleton microtubule towards the minus end of microtubules, which is usually oriented towards the cell center. Thus they are called “minus cell directed motor”. While kinesin motor protein that move towards the microtubules plus end, are called “plus end directed motors”. Dynein cells be divided into two groups, 1) cytoplamic dynein 2) axonamal dynein. Which are also called ciliary or flagella dynein.

Function :- Axonamal dynein causes sliding of microtubules in the axonamal of cillia and flagella and is found only in cells that those structures. Cytoplasmic dynein, found in all animal cells and possibly plant cells as well performs functions necessary for cell survival such as organelle transport and centrosome assemly. Cytoplamic dynein probably moves processively along the microtubule, that is one or the other of its stalk is always attach to the microtubule so that the dynein can walk a considerable distant along a tubule without detaching. Cytoplasmic dynein probably helps to position the golgi complex and other organelles in the cell, it also help transport cargo needed for cell functioning such as visicals made by the endoplasmic reticulum, endosomes, and lysosomes. Dynein is also probably involve in the movement of chromosomes and positioning the mitotic spindles for cell division. Dynein carries orgenelles and microtubules fragements along the axons of neurons in a process called “axoplasmic transport”. It also carry HIV to the nuclie of cells that have been infected.

Structure :-Each molecules of the dynein motor is the

complex of the assembly composed of many smaller polypeptide subunits cytoplasmic and axonamal dynein contain some of the same components but they also contain some unique subunit.

1)Cytoplasmic dynein :- cytoplasmic dynein which has a molecular

mass of 1500 kilodeltons contains approximately 12 polypeptide subunit; “two identical” heavy chain 520 KD in mass which contain the ATPase activity and are thus responsible for generating movements along the microtubules; two 74 KD intermediate chain which are believe to enter the dynein to its cargo; four 53-59 KD intermediate chains and several light chain which are less well understood. The force generating ATPase activity of dynein heavy chain is located in its large doughnut shape head which is related to other ‘AAA’ protein while two projection from the head contected to other cytoplasmic stucture.

Dyenin & MicrotubulesDyenin & Microtubules

One projection the coiled-coil stalk, binds to and walks along the surface of the microtubules via or repeated cycle of detachment and reattachment. The other projection the extended tail (also called steam) binds to the intermediate and light chain subunits which attach the dynein to its cargo. The alternating activity of the paired heavy chain in the complete cytoplasmic dynein motor enables a single dynein molecule to transport its cargo by walking the considerable distant along a microtubule without becoming completely detached. In eukyryotes cytoplasmic dynein must be actiated by binding of dynactin another multisubunit protein which is essential for mitosis. Dynactin may regulate the activity of the dynein and possibly facilitate the attachment of dynein to its cargo.2) Axonal dynein :-Axonal dynein come in multiple forms that contain either one, two or three non identical heavy chain, each heavy chain has globular motor domain with a doughnut shaped structure believe to resembles that of other AAA protein.

Microtubules :-Microtubules, an integral component of the cellular cytoskeleton, consist of cytoplasmic tubes 25 nm in diameter and often of extreme length. Microtubules are necessary for the formation and function of the mitotic spindle and thus are present in all eukaryotic cells. They are also involved in the intracellular movement of endocytic and exocytic vesicles and form the major structural components of cilia and flagella. Microtubules are a major component of axons and dendrites, in which they maintain structure and participate in the axoplasmic flow of material along these neuronal processes.Structures:-Microtubules are cylinders of 13 longitudinally arranged protofilaments, each consisting of dimers of α-tubulin and β-tubulin, closely related proteins of approximately 50 kDa molecular mass. The tubulin dimers assemble into protofilaments and subsequently into sheets and then cylinders.

A microtubules-organizing center, located around a pair of centrioles,nucleastes the growth of new microtubules. A third species of tubulin, γ-tubulin, appears to play an important role in this assembly. GTP is required for assembly. A variety of protein are associated with microtubules (microtubule-associated protein[MAPs], one of which is tau) and play important roles in microtubules assembly and stabilization. Microtubules are in a state of dynamic instability, constantly aseembling and disassembling. They exhibit polarity (plus and minus ends); this is important in their growth from centrioles and in their ability to direct intracellular movement. For instance, in axonal transport, the protein kinesin, with a myosin-like ATPase activity, uses hyrolysis of ATP to move vesicles down the axon toward the positive end of the microtubules formation. Flow of materials in the opposite direction, toward the negative end, is powered by cytosolic dynein,another protein with ATPase activity. Certain drugs acts on microtubules, like colchicin, vinblastin and griseofulvin by interfering with their assembly or disassembly.

ATP synthaseATP synthase :-An ATP synthase is a general term for an enzyme that can synthesize adenosine triphosphate (ATP) from adenosine diphosphate (ADP) & inorganic phosphate by utilizing some form of energy. The overall reaction sequence is :- ADP + Pi ATPThese enzmes are of crucial importance in almost all organisms, because ATP is the common “energy currency” of cells.Structure & nomenclature :- The Fo portion is within the membrane The F1 portion of the ATP synthase is above the membrane.It’s easy to visualize the FoF1 particle as resembling the fruiting body of a common mushroom, with the head being the F1 particle, the stalk being the gamma subunit of F1, and the base and roots being the Fo particle embeded in the membrane. The F1 fraction derives it name from the term “fraction 1” and Fo (written as a subscript “O”, not “zero”)derives it name from being oligomycin binding fraction.

ATP synthaseATP synthase

The Crystal structure of the F1 showed alternating alpha and beta subunit (3 of each), arrange like segments of an orange around an asymmetrical gamma subunit. According to the current model of ATP synthesis (known as the alternating catalytic model), the proton motive force across the inner mitochondrial membrane, generated by the electron transport chain, drives the passage of proton through the membrane the Fo region of ATP synthase. A portion of Fo (the ring of C-subunits) rotate as the protons pass through the membrane. The C ring is the tightly attach to the asymmetrical central stalk (consisting primarily of the gamma subunit) which rotates within the alpha 3 beta 3 of F1 causing the 3 catalytic nucleotide binding site to go through a series of conformational changes that leads to ATP synthesis. The major F1 subunits are prevented from rotating sympathy with the central stalk rotor by a peripheral stalk that joined the alpha 3 beta 3 to the non rotating portion of Fo. The structure of the intact ATP sythase is currently known at low resolution from electrocryo-microscopy(cryo-EM) studies of the complex.

The cryo-EM model of ATP synthase shows that the peripheral stalk is a flexible rope like structure that wraps around the complex as it joins F1 to Fo. Under the right condition, the enzyme reaction can also carried out in reverse, with ATP hydrolysis driving proton pumping across the membrane. The binding change mechanism involves the active site of a beta subunit cycling between 3 states. In the “open” state, ADP and phosphate enter the active site, in the diagram it is shown in brown. The protein then close up around the nucleus and bind them loosely-the “loose” state (shown in red). The enzyme then under goes another change in shape and forces this molecules together, with the active site in the resulting “tight” state( shown in pink) binding the newly produce ATP molecules with very high affinity. Finally the active cycle back to the open state, releasing ATP and binding more ADP and phosphate, ready for the next cycle of ATP production.

Physiological Role :-Like other enzymes, the activity of F1 Fo ATP synthase is reversible large enough quantity of ATP causes it to create a transmembrane proton gradient, this is used by fermenting bacteria which do not have an electron transport chain, and hydrolyze ATP to make a proton gradient, which they used for flagella and transport of nutrient into the cell. In respiring bacteria under physiological condition, ATP synthase generally runs in the opposite direction, creating ATP while using the proton motive force created by the electron transport chain as a source of energy. The over all process of creating energy in this fashion is termed oxidative phosphorylation. The same process take place in mitochondria where ATP synthase is located in the inner mitochondrial membrane ( so the F1 part sticks into mitochondrial metrix, where ATP synthesis take place).

Nanobot :- Nanobot, or nanorobot or nanite, sometimes called nanoagent, imaginary machine (robot) on a scale of few to few hundreds of nanometers designed to perform specific tasks. Some (e.g. E Drexler) envision nanobots destroying cancer cells, ‘picking up’ specific molecules (e.g. radicals) repairing damage at the cellular level and similar. The prototype models for the most of these futuristic concepts are specific cells (e.g. phagocytes which ingest foreign matter) and cellular molecular machineries. (e.g. RNA polymerase, ribosome). Interestingly and amusingly enough ‘nano-probes’ are a part of The Borg technology in star track serial. A very popular type of nanobots are those that have the ability to replicate themselves. ( replicators, self assembler…).

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