| Autor: |
Díez, Eliecer, Álvaro, Josué, Espeso, Eduardo A., Rainbow, Lynne, Suárez, Teresa, Tilburn, Joan, Arst Jr, Herbert N., Peñalva, Miguel Á. |
| Předmět: |
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| Zdroj: |
EMBO Journal; 3/15/2002, Vol. 21 Issue 6, p1350-1359, 10p |
| Abstrakt: |
The Aspergillus PacC transcription factor undergoes proteotytic activation in response to alkaline ambient pH. In acidic environments, the 674 residue translation product adopts a 'closed' conformation, protected from activation through intramolecular interactions involving the ⩽150 residue C-terminal domain. pH signalling converts PacC to an accessible conformation enabling processing cleavage within residues 252-254. We demonstrate that activation of PacC requires two sequential proteotytic steps. First, the 'closed' translation product is converted to an accessible, committed intermediate by proteolytic elimination of the C-terminus. This ambient pH-regulated cleavage is required for the final, pH-independent processing reaction and is mediated by a distinct signalling protease (possibly PaIB). The signalling protease cleaves PacC between residues 493 and 500, within a conserved 24 residue 'signalling protease box'. Precise deletion or Leu498Ser substitution prevents formation of the committed and processed forms, demonstrating that signalling cleavage is essential for final processing. In contrast, signalling cleavage is not required for processing of the Leu340Ser protein, which tacks interactions preventing processing. In its two-step mechanism, PacC processing can be compared with regulated intramembrane proteolysis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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