PMID: 16601115

 

    Legend: Sugar

Title : Structural basis of reduction-dependent activation of human cystatin F . Cystatins are important natural cysteine protease inhibitors targeting primarily papain-like cysteine proteases, including cathepsins and parasitic proteases like cruzipain, but also mammalian asparaginyl endopeptidase

Abstract :
  1. Mammalian cystatin F , which is expressed almost exclusively in hematopoietic cells and accumulates in lysosome-like organelles, has been implicated in the regulation of antigen presentation and other immune processes
  2. It is an unusual cystatin superfamily member with a redox-regulated activation mechanism and a restricted specificity profile
  3. We describe the 2.1A crystal structure of human cystatin F in its dimeric "off" state
  4. The two monomers interact in a fashion not seen before for cystatins or cystatin-like proteins that is crucially dependent on an unusual intermolecular disulfide bridge, suggesting how reduction leads to monomer formation and activation
  5. Strikingly, core sugars for one of the two N-linked glycosylation sites of cystatin F are well ordered, and their conformation and interactions with the protein indicate that this unique feature of cystatin F may modulate its inhibitory properties, in particular its reduced affinity toward asparaginyl endopeptidase compared with other cystatins