A disintegrin and metalloproteinase

The ADAM metalloproteases ( engl. A Disintegrin And Metalloproteinase = " a disintegrin and metalloproteinase " ), are a group of enzymes belonging to the Metzinkinen - include - a subclass of metalloproteinases. As a cofactor a zinc ion is required. So far, over 30 ADAM orthologues are known. In addition there are splice variants.

Construction

ADAM metalloproteases are integral transmembrane proteins of type I ( single pass ). They are usually from 800 to 1200 amino acids. The C-terminus is located in the intracellular space. It is followed by the transmembrane region, which in some ADAMs followed by an EGF -like domain in the extracellular space. The following cysteine-rich domain is followed by the disintegrin domain. Then comes the metalloprotease domain. A pro-domain with the N-terminus completes the ADAM protein. The prodomain must be cleaved for activation of the enzyme. The prodomain disables the metalloprotease domain by a cysteine ​​switch ( cysteine ​​switch). Conserved cysteine ​​residues in the pro-domain, in addition to coordinate the function of the enzyme necessary for the zinc ion ( Zn2 ) in the metalloprotease domain. Thus, the metalloprotease domain is in an inactive conformation, causing the entire enzyme is deactivated. By furin or other proprotein convertases, the pro-domain can be cleaved, whereby the zinc ion is coordinated by the only metalloprotease domain, and so the enzyme is activated.

By stronger complexing agents such as EDTA, zinc is bound, and the ADAM protease ( reversible) has been deactivated.

The disintegrin domain gets its name because of the high structural analogy to the disintegrins in snake venoms ( snake venom metalloprotease, SVMP ).

Function

On a number of cell biological processes, the ADAM metalloproteases are directly involved. Thus, they play an important role, for example in membrane fusion, the development of muscles, cell differentiation, cell migration and inflammatory responses. When cutting other transmembrane proteins, known as ectodomain shedding, the ADAMs are also involved. For example, the amyloid precursor protein (APP ) is the ADAM metalloproteases ADAM9, ADAM10 and ADAM17 - which belong to the α - secretases - "right " fit.

Of the known human proteases ADAM twelve proteolytic activity is predicted. Yet even the proteolytic activity was measured only in the half of it. The selectivity or specificity of the ADAM proteases is not yet secured. Some ADAMs belong to the sheddases.

Occurrence

In all vertebrates, see the ADAM metalloproteases. Also, the model organism Caenorhabditis elegans, Drosophila and Xenopus cells express ADAM. However, they are not found on the cell membranes of Escherichia coli and Saccharomyces cerevisiae. In plants, they are not present. The individual ADAMs are differentially expressed depending on the cell type.