Cyclin-Dependent Kinase

About Cyclin-Dependent Kinase / CDK:

 Cyclin-Dependent Kinase is a protein family that has a crucial role in regulating a cell cycle, differentiating nerve cells and mRNA processing.

Cyclin-Dependent Kinase Function
First, CDK has been known for its importance in the cell cycle, and then by extension in proliferation. However, it has been found that yeast cells can normally proliferate if you replace their CDK gene with a homologous human gene. CDK also binds cyclins, and without cyclins, there is little kinase activity in CDK. Animals are known to have at least 9 CDKs in their body, and four of these are involved in cell cycle regulation. yet, in some mammals, CDK1 with A2 and B1 can drive the cell alone, meaning that the other strands are not necessary here. CDK and its different cyclin partners can also have different effects on animals. For example, one study used mice to test the CDK and partners effects and found that CDK4 with its partner Cyclin D in the G1 phase, can have impacts such as infertility and diabetes.

CDK Structure
Being small proteins, and only have weights of around 34 to 40 KDA with little more than a kinase domain. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate involves 5 elements. S/T is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine. This complex protein is formed by an inactive catalytic subunit of protein kinase, which is CDK, binds to a regulatory subunit known as cyclin. When these two associates with one another, they create Cyclin-Dependent Kinase Complex.

Cyclin-Dependent Kinase Mechanism
In order for CDKs to be active, they need to be free of CDK inhibitor proteins known as CDIs. This is activated by CDK activating kinase (CAK) which phosphorylates threonine residue at 160 in the activation loop. CAK is used as a regulator of certain CDK types and is a member of the CDK family. For this reason, it is thought that CAK is indirectly regulated by a cyclin, meaning that in some ways, it is also dependent on cyclin. However, this is usually reversible, although the levels of CAK do remain high throughout the entire cell cycle.

CDK Interactions
The ATP-binding site, of all kinases, is a cleft between a small amino-terminal lobe and a larger carboxy-terminal lobe. The structure of human Cdk2 shows that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. Without cyclin, a flexible loop forms known as the activation loop, and this blocks the cleft meaning that the position of some of the key amino acids is not going to be right for ATP binding. Cyclin is needed for the two alpha-helices to change their position and allow for ATP binding without an issue. One of these helices is the L12 which comes right before the activation loop, which rearranges the loop, allowing for the ATP binding to take place.