PROSITE documentation PDOC51688

Intramolecular chaperone auto-processing (ICA) domain profile

The Intramolecular Chaperone Auto-processing (ICA) [1] domain, also called Intramolecuar Chaperone Domain (ICD) [2] or C-terminal Intramolecular Chaperone Domain (CIMCD) [3], is capable of catalyzing trimerization-dependent auto-proteolysis. The ICA domain contains two absolutely conserved serine and lysine residues. They form a catalytic dyad that mediates cleavage at the serine residue. The correct positioning of these catalytic residues, along with an arginine residue that stabilizes the oxyanion during the peptide bond breakage, is thought to be achieved only upon folding and trimerization, enabling the ICA domain to function as a folding sensor. The ICA domain belongs to peptidase family S74 [E1].

The ICA domain displays an α1-β1-α2-β2-α3-β3-β4-α4 fold (see <PDB:3GUD>). The ICA domain homotrimer has a jellyfish-like outline with a central threefold symmetry axis and mainly consists of α-helices. It comprises a quite globular core and an extended loop region, reminiscent of tentacles, protruding from the center. The central part of the core is a slightly twisted three helix bundle, forming the trimerization interface [3].

Some proteins known to contain an ICA domain are listed below:

• Animal myelin regulatory factor (MYRF), a key transcriptional regulator for of oligodendrocyte differenciation and central nervous system (CNS) myelination. The MYRF protein undergoes an activating cleavage event to release the functional transcription factor from the transmembrane domain that otherwise anchors it to the endoplasmic reticulum [1,2].
• Tailed bacteriophage (Caudovirus) endosialidases, the tailspike proteins essential for bacteriophages to infect bacteria encapsulated with polysaccharides.

The profile we developed covers the entire ICA domain.