Model of the tetramerization domain of AChE

The 'tailed' heteromeric molecules are the most physiologically important forms of AChE, and the predominant forms in brain and at neuromuscular junctions. Massoulie and colleagues pinpointed a small proline-rich attachment domain (PRAD), around which the globular subunits assemble to form tetramers. The critical feature of this 17-residue peptide is the presence of three and five consecutive prolines; thus even synthetic polyproline can replace the natural PRAD.
Similarly, a well-conserved 40-residue peptide at the C-terminus of the AChE subunit sufficies to form the same quarternary organization by interacting with PRAD. This portion of AChE contains a series of seven aromatic residues, including three equally spaced Trp residues. Thus, it was named the 'tryptophan amphiphilic tetratmerization' (WAT) domain. We have crystallized a complex of this WAT/PRAD complex (ratio 4:1), with selenomethionine incorporated, and plan to determine its structure using MAD.

Based on the WAT/PRAD crsystaql structre a full model of the physiological ColQ‐linked AChET tetramer was built. The ColQ polypeptide is vertical. The WAT polypeptides are displayed as ribbons, and the PRAD as a yellow surface model. Subunit color coding is the same as used for WAT chains.