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A four‐to‐one association between peptide motifs: four C‐terminal domains from cholinesterase assemble with one proline‐rich attachment domain (PRAD) in the secretory pathway
Author(s) -
Simon Stéphanie,
Krejci Eric,
Massoulié Jean
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.21.6178
Subject(s) - biology , terminal (telecommunication) , proline , peptide , association (psychology) , peptide sequence , c terminus , domain (mathematical analysis) , cholinesterase , biochemistry , microbiology and biotechnology , genetics , amino acid , gene , endocrinology , telecommunications , mathematical analysis , philosophy , mathematics , epistemology , computer science
The major type of acetylcholinesterase in vertebrates (AChE T ) is characterized by the presence of a short C‐terminal domain of 40 residues, the ‘tryptophan amphiphilic tetramerization’ (WAT) domain. The presence of this domain is not necessary for catalytic activity but is responsible for hydrophobic interactions and for the capacity of AChE T subunits to form quaternary associations with anchoring proteins, thereby conditioning their functional localization. In the collagen tail of asymmetric forms, we characterized a small conserved region that is sufficient for binding an AChE T tetramer, the proline‐rich attachment domain (PRAD). We show that the WAT domain alone is sufficient for association with the PRAD, and that it can attach foreign proteins (alkaline phosphatase, GFP) to a PRAD‐containing construct with a glycophosphatidylinositol anchor (GPI), and thus anchor them to the cell surface. Furthermore, we show that isolated WAT domains, or proteins containing a WAT domain, can replace individual AChE T subunits in PRAD‐linked tetramers. This suggests that the four WAT domains interact with the PRAD in a similar manner. These quaternary interactions can form without intercatenary disulfide bonds. The common catalytic domains of AChE are not necessary for tetrameric assembly, although they may contribute to the stability of the tetramer.