6h5t: Difference between revisions
New page: '''Unreleased structure''' The entry 6h5t is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Intersectin SH3A short isoform== | |||
<StructureSection load='6h5t' size='340' side='right'caption='[[6h5t]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6h5t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H5T FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7PG:2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL'>7PG</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITSN1, ITSN, SH3D1A ([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=6h5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h5t OCA], [http://pdbe.org/6h5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h5t RCSB], [http://www.ebi.ac.uk/pdbsum/6h5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h5t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/ITSN1_HUMAN ITSN1_HUMAN]] Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1.<ref>PMID:11744688</ref> <ref>PMID:22648170</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The scaffolding protein intersectin 1 plays important roles in clathrin-mediated endocytosis and in the replenishment of release-ready synaptic vesicles (SV). Two splice variants of intersectin's SH3A domain are expressed in the brain, and association of the neuron-specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C-terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N-terminal intramolecular sequence that operates synergistically with the C-terminal motif. NMR spectroscopic investigations show that the five-amino acid insertion into the beta strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N-terminal sequence. The difference in the autoregulatory mechanism of the domain's variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction networks. | |||
Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain.,Gerth F, Japel M, Sticht J, Kuropka B, Schmitt XJ, Driller JH, Loll B, Wahl MC, Pagel K, Haucke V, Freund C Structure. 2019 Apr 9. pii: S0969-2126(19)30116-9. doi:, 10.1016/j.str.2019.03.020. PMID:31031201<ref>PMID:31031201</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6h5t" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Driller, J H]] | |||
[[Category: Freund, C]] | |||
[[Category: Gerth, F]] | |||
[[Category: Loll, B]] | |||
[[Category: Wahl, M C]] | |||
[[Category: Endocytosis]] | |||
[[Category: Intersectin 1]] | |||
[[Category: Sh3 domain]] | |||
[[Category: Splice isoform]] | |||
Latest revision as of 16:34, 10 May 2019
Intersectin SH3A short isoformIntersectin SH3A short isoform
Structural highlights
Function[ITSN1_HUMAN] Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1.[1] [2] Publication Abstract from PubMedThe scaffolding protein intersectin 1 plays important roles in clathrin-mediated endocytosis and in the replenishment of release-ready synaptic vesicles (SV). Two splice variants of intersectin's SH3A domain are expressed in the brain, and association of the neuron-specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C-terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N-terminal intramolecular sequence that operates synergistically with the C-terminal motif. NMR spectroscopic investigations show that the five-amino acid insertion into the beta strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N-terminal sequence. The difference in the autoregulatory mechanism of the domain's variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction networks. Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain.,Gerth F, Japel M, Sticht J, Kuropka B, Schmitt XJ, Driller JH, Loll B, Wahl MC, Pagel K, Haucke V, Freund C Structure. 2019 Apr 9. pii: S0969-2126(19)30116-9. doi:, 10.1016/j.str.2019.03.020. PMID:31031201[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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