Tetramerization domain of acetylcholinesterase
From Proteopedia
STRUCTURE OF THE TETRAMERIZATION DOMAIN OF ACETYLCHOLINESTERASE: FOUR-FOLD INTERACTION OF A WWW MOTIF WITH A LEFT-HANDED POLYPROLINE HELIX
Contents |
Overview
Functional localization of acetylcholinesterase (AChE) in vertebrate muscle and brain depends on interaction of the tryptophan amphiphilic tetramerization sequence at the C-terminus of its major splice variant (T) with a proline-rich attachment domain of the anchoring proteins collagenous (ColQ) and proline-rich membrane anchor. The crystal structure of the reveals a novel supercoil structure in which four parallel WAT chains form a left-handed superhelix around an antiparallel left-handed PRAD helix resembling polyproline II. The WAT coiled coils possess a WWW motif making repetitive hydrophobic stacking and hydrogen-bond interactions with the PRAD. The WAT chains are related by an approximately 4-fold screw axis around the PRAD. Each WAT makes similar but unique interactions consistent with an asymmetric pattern of disulfide linkages between the AChE tetramer subunits and ColQ. The P59Q mutation in ColQ, which causes congenital endplate AChE deficiency and is located within the PRAD, disrupts crucial WAT-WAT and WAT-PRAD interactions. (model coordinates)
Disease
Known diseases associated with this structure: Blood group, Yt system OMIM:[100740], Endplate acetylcholinesterase deficiency OMIM:[603033]
About this Structure
1VZJ is a Protein complex structure of sequences from Homo sapiens. Active as Acetylcholinesterase, with EC number 3.1.1.7 Full crystallographic information is available from OCA.
Reference
The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix., Dvir H, Harel M, Bon S, Liu WQ, Vidal M, Garbay C, Sussman JL, Massoulie J, Silman I, EMBO J. 2004 Nov 10;23(22):4394-405. Epub 2004 Nov 4. PMID:15526038
Created with the participation of Eran Hodis, Michal Harel, Joel L. Sussman, Jaime Prilusky.
