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 PubMed
Optogenetic and chemogenetic control of proteins has revealed otherwise inaccessible facets of signaling dynamics. Here, we use light- or ligand-sensitive domains to modulate the structural disorder of diverse proteins, thereby generating robust allosteric switches. Sensory domains were inserted into nonconserved, surface-exposed loops that were tight and identified computationally as allosterically coupled to active sites. Allosteric switches introduced into motility signaling proteins (kinases, guanosine triphosphatases, and guanine exchange factors) controlled conversion between conformations closely resembling natural active and inactive states, as well as modulated the morphodynamics of living cells. Our results illustrate a broadly applicable approach to design physiological protein switches.
Engineering extrinsic disorder to control protein activity in living cells.,Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan NV, Hahn KM Science. 2016 Dec 16;354(6318):1441-1444. PMID:27980211[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jenna S, Hussain NK, Danek EI, Triki I, Wasiak S, McPherson PS, Lamarche-Vane N. The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin. J Biol Chem. 2002 Feb 22;277(8):6366-73. Epub 2001 Dec 13. PMID:11744688 doi:http://dx.doi.org/10.1074/jbc.M105516200
- ↑ Teckchandani A, Mulkearns EE, Randolph TW, Toida N, Cooper JA. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis. Mol Biol Cell. 2012 Aug;23(15):2905-16. doi: 10.1091/mbc.E11-12-1007. Epub 2012, May 30. PMID:22648170 doi:10.1091/mbc.E11-12-1007
- ↑ Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan NV, Hahn KM. Engineering extrinsic disorder to control protein activity in living cells. Science. 2016 Dec 16;354(6318):1441-1444. PMID:27980211 doi:http://dx.doi.org/10.1126/science.aah3404
