1zl8

From Proteopedia

(Difference between revisions)

Revision as of 09:06, 20 January 2021

NMR structure of L27 heterodimer from C. elegans Lin-7 and H. sapiens Lin-2 scaffold proteins

Structural highlights

1zl8 is a 2 chain structure with sequence from Caeel and Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1rso, 1vf6, 1y74, 1y76
Gene:	LIN7 (CAEEL), CASK, LIN2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CSKP_HUMAN] Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:300749]. A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.^[1] Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.^[2]

Function

[CSKP_HUMAN] Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1.

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

LIN-2/7 (L27) domains are protein interaction modules that preferentially hetero-oligomerize, a property critical for their function in directing specific assembly of supramolecular signaling complexes at synapses and other polarized cell-cell junctions. We have solved the solution structure of the heterodimer composed of the L27 domains from LIN-2 and LIN-7. Comparison of this structure with other L27 domain structures has allowed us to formulate a general model for why most L27 domains form an obligate heterodimer complex. L27 domains can be divided in two types (A and B), with each heterodimer comprising an A/B pair. We have identified two keystone positions that play a central role in discrimination. The residues at these positions are energetically acceptable in the context of an A/B heterodimer, but would lead to packing defects or electrostatic repulsion in the context of A/A and B/B homodimers. As predicted by the model, mutations of keystone residues stabilize normally strongly disfavored homodimers. Thus, L27 domains are specifically optimized to avoid homodimeric interactions.

A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes.,Petrosky KY, Ou HD, Lohr F, Dotsch V, Lim WA J Biol Chem. 2005 Nov 18;280(46):38528-36. Epub 2005 Sep 7. PMID:16147993^[3]

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

References

↑ Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet. 2008 Sep;40(9):1065-7. doi: 10.1038/ng.194. PMID:19165920 doi:10.1038/ng.194
↑ Piluso G, D'Amico F, Saccone V, Bismuto E, Rotundo IL, Di Domenico M, Aurino S, Schwartz CE, Neri G, Nigro V. A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet. 2009 Feb;84(2):162-77. doi: 10.1016/j.ajhg.2008.12.018. Epub 2009, Feb 5. PMID:19200522 doi:10.1016/j.ajhg.2008.12.018
↑ Petrosky KY, Ou HD, Lohr F, Dotsch V, Lim WA. A general model for preferential hetero-oligomerization of LIN-2/7 domains: mechanism underlying directed assembly of supramolecular signaling complexes. J Biol Chem. 2005 Nov 18;280(46):38528-36. Epub 2005 Sep 7. PMID:16147993 doi:10.1074/jbc.M506536200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zl8"

@@ Line 1: / Line 1: @@
 ==NMR structure of L27 heterodimer from C. elegans Lin-7 and H. sapiens Lin-2 scaffold proteins==
-<StructureSection load='1zl8' size='340' side='right' caption='[[1zl8]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='1zl8' size='340' side='right'caption='[[1zl8]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1zl8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZL8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZL8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1zl8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZL8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ZL8 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rso|1rso]], [[1vf6|1vf6]], [[1y74|1y74]], [[1y76|1y76]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rso|1rso]], [[1vf6|1vf6]], [[1y74|1y74]], [[1y76|1y76]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LIN7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL]), CASK, LIN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1zl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zl8 OCA], [http://pdbe.org/1zl8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zl8 RCSB], [http://www.ebi.ac.uk/pdbsum/1zl8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zl8 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1zl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zl8 OCA], [http://pdbe.org/1zl8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zl8 RCSB], [http://www.ebi.ac.uk/pdbsum/1zl8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zl8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 37: / Line 37: @@
 [[Category: Caeel]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Dotsch, V]]
 [[Category: Lim, W A]]

1zl8

From Proteopedia

Revision as of 09:06, 20 January 2021

NMR structure of L27 heterodimer from C. elegans Lin-7 and H. sapiens Lin-2 scaffold proteins

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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