1VZJ

Structure of the tetramerization domain of acetylcholinesterase: four-fold interaction of a WWW motif with a left-handed polyproline helix

Summary for 1VZJ

• Entry DOI: 10.2210/pdb1vzj/pdb
• Related: 1B41 1F8U 2CLJ
• Descriptor: ACETYLCHOLINESTERASE, ACETYLCHOLINESTERASE COLLAGENIC TAIL PEPTIDE (3 entities in total)
• Functional Keywords: hydrolase, acetylcholinesterase, synapse, neurotransmitter degradation, alternative splicing, disease mutation.
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 10
• Total formula weight: 44397.43

Authors

Dvir, H.,Harel, M.,Bon, S.,Liu, W.-Q.,Vidal, M.,Garbay, C.,Sussman, J.L.,Massoulie, J.,Silman, I. (deposition date: 2004-05-20, release date: 2005-01-10, Last modification date: 2019-10-16)

Primary citation

Dvir, H.,Harel, M.,Bon, S.,Liu, W.-Q.,Vidal, M.,Garbay, C.,Sussman, J.L.,Massoulie, J.,Silman, I.
The Synaptic Acetylcholinesterase Tetramer Assembles Around a Polyproline-II Helix
Embo J., 23:4394-, 2004

PubMed Abstract: Functional localization of acetylcholinesterase (AChE) in vertebrate muscle and brain depends on interaction of the tryptophan amphiphilic tetramerization (WAT) sequence, at the C-terminus of its major splice variant (T), with a proline-rich attachment domain (PRAD), of the anchoring proteins, collagenous (ColQ) and proline-rich membrane anchor. The crystal structure of the WAT/PRAD complex 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. A model is proposed for the synaptic AChE(T) tetramer.

PubMed: 15526038
DOI: 10.1038/SJ.EMBOJ.7600425

Experimental method

X-RAY DIFFRACTION (2.35 Å)