A great number of physiological processes are regulated by the release of ectodomains of membrane proteins. A Disintegrin And Metalloprotease
17 (ADAM
17) is one of the important enzymes, which mediate this process called shedding. Today, more than 70 substrates of this transmembrane metalloprotease are known. This broad spectrum raises the question how ADAM
17 recognizes its substrates specifically. Differently tagged ADAM
17 deletion variants were used to demonstrate that exclusively the extracellular domains of ADAM
17 are needed for interaction with two of its substrates, the
IL-6R and the IL-1RII; whereas the transmembrane- and cytoplasmic-region are dispensable for this process. In the extracellular part solely the membrane-proximal domain of ADAM
17 is mandatory for recognition of the two type-I transmembrane proteins, but not for the interaction with the type-II transmembrane molecule TNF-伪.
Structured summary of protein interactions
with by () with by ()