1vzj

From Proteopedia

(Difference between revisions)

Revision as of 07:28, 4 April 2018

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

Structural highlights

1vzj is a 10 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	1b41, 1f8u, 2clj
Activity:	Acetylcholinesterase, with EC number 3.1.1.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[COLQ_HUMAN] Defects in COLQ are the cause of congenital myasthenic syndrome Engel type (CMSE) [MIM:603034]; also known as end-plate acetylcholinesterase deficiency or congenital myasthenic syndrome type IC (CMS-IC). CMSE is a rare autosomal recessive congenital myasthenic syndrome characterized by onset during childhood, generalized weakness, abnormal fatigability on exertion, refrectoriness to acetylcholinesterase drugs, decremental electromyographic response and morphological abnormalities of the neuromuscular junctions.^[1] ^[2]

Function

[ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.^[3] ^[4] ^[5] ^[6] [COLQ_HUMAN] Anchors the catalytic subunits of asymmetric AChE to the synaptic basal lamina.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Donger C, Krejci E, Serradell AP, Eymard B, Bon S, Nicole S, Chateau D, Gary F, Fardeau M, Massoulie J, Guicheney P. Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). Am J Hum Genet. 1998 Oct;63(4):967-75. PMID:9758617
↑ Ohno K, Engel AG, Brengman JM, Shen XM, Heidenreich F, Vincent A, Milone M, Tan E, Demirci M, Walsh P, Nakano S, Akiguchi I. The spectrum of mutations causing end-plate acetylcholinesterase deficiency. Ann Neurol. 2000 Feb;47(2):162-70. PMID:10665486
↑ Chhajlani V, Derr D, Earles B, Schmell E, August T. Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. FEBS Lett. 1989 Apr 24;247(2):279-82. PMID:2714437
↑ Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A. The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. J Biol Chem. 1991 Dec 15;266(35):23977-84. PMID:1748670
↑ Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al.. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem. 1992 Sep 5;267(25):17640-8. PMID:1517212
↑ Yang L, He HY, Zhang XJ. Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci Res. 2002 Apr;42(4):261-8. PMID:11985878
↑ Dvir H, Harel M, Bon S, Liu WQ, Vidal M, Garbay C, Sussman JL, Massoulie J, Silman I. The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix. EMBO J. 2004 Nov 10;23(22):4394-405. Epub 2004 Nov 4. PMID:15526038 doi:7600425

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1vzj"

@@ Line 1: / Line 1: @@
-==STRUCTURE OF THE TETRAMERIZATION DOMAIN OF ACETYLCHOLINESTERASE: FOUR-FOLD INTERACTION OF A WWW MOTIF WITH A LEFT-HANDED POLYPROLINE HELIX==
+==Structure of the tetramerization domain of acetylcholinesterase: four-fold interaction of a WWW motif with a left-handed polyproline helix==
 <StructureSection load='1vzj' size='340' side='right' caption='[[1vzj]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b41|1b41]], [[1f8u|1f8u]], [[2clj|2clj]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vzj OCA], [http://pdbe.org/1vzj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vzj RCSB], [http://www.ebi.ac.uk/pdbsum/1vzj PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vzj OCA], [http://pdbe.org/1vzj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vzj RCSB], [http://www.ebi.ac.uk/pdbsum/1vzj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vzj ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vz/1vzj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vz/1vzj_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1vzj ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 33: / Line 34: @@
 ==See Also==
-*[[Acetylcholinesterase|Acetylcholinesterase]]
+*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
 == References ==
 <references/>
@@ Line 48: / Line 49: @@
 [[Category: Sussman, J L]]
 [[Category: Vidal, M]]
+[[Category: Alternative splicing]]
 [[Category: Disease mutation]]
 [[Category: Hydrolase]]
 [[Category: Neurotransmitter degradation]]
 [[Category: Synapse]]

1vzj

From Proteopedia

Revision as of 07:28, 4 April 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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