Sandbox myosinkinesin

This is a default text for your page Sandbox myosinkinesin. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

This is 4UXR.

Function

Kinesin is generally responsible for the transport of polypeptides and other large molecules throughout a single cell, such as moving the spindles during cell division. Kinesin can only move from the negative (-) end of microtubules to the positive (+) end. This means that kinesin only moves objects out towards the periphery of the cell and thus aids in the secretion of molecules or division of cells.

Disease

Kinesin are involved during mitosis, failure of kinesin to work properly can lead to trisomy and other meiosis/mitosis related diseases.

Structural highlights

Heavy Chain:

It is the most conserved region amongst kinesin which consists of the head, neck, and tail. Usually contains eight core β-sheets and six major alpha helixes, most of these secondary structures are in different places in the primary sequence but line up in the tertiary structure.

Here is a picture of the light chains.

Light Chain: Not technically part of the protein of kinesin or myosin itself, but its presence is necessary for activity. It regulates conformational changes within the protein.

Head: Most conserved domain amongst all kinesin, it consists mainly of alpha helixes. Its tertiary structure usually includes a large cleft from the actin binding site to the ATP binding pocket. The head has the ability to bind microtubule on one site and bind ATP at another. This section undergoes the most conformational change and is responsible for the force that causes kinesin to move along the cytoskeleton. In kinesin, binding of ATP appears to have allosteric control over the binding of kinesin to the tubules, by a twisting of a β- sheet core, showing allosteric control between the subdomains within the protein.

ATPase: It generates this force using an ATPase either coupled with the myosin/kinesin or inherent within the head, the inherent ATPase uses a P-loop, which is a phosphate- binding loop used in adenylate kinase, Ras, and others. Both also create a similar environment for the γ-phosphate, which uses a conserve motif of Ser-Ser-Arg.

In kinesin, the binding of ATP greatly increases the binding of kinesin to the microtubules, to allow it to perform a power stroke. The cleft uses His 93, Pro 17 and Arg 16 to hold ATP. The lack of these loops allows kinesin to react with ATP much faster.

RAS fold: conserved domain among many signaling proteins. A structural motif where a nucleotide molecule is bound to loops at one end of a β-sheet domain. This suggests that myosin and kinesin may have evolved from a common ancestor.

Neck:

completely alpha-helical region between the head and the tail on the heavy chain that binds to the light chains.

In kinesin, the neck region of amino acids 330-370 generally form a coiled coil region that is long and flexible.

Tail:

Includes polypeptide binding site, varies the most since it is responsible for dictating the location within the cell that the protein is active.