Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

Handle URI:
http://hdl.handle.net/10754/623363
Title:
Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow
Authors:
Aleisa, Fajr A; Sakashita, Kosuke ( 0000-0002-7118-5511 ) ; Lee, Jaeman; Abu Samra, Dina Bashir Kamil ( 0000-0002-0974-5362 ) ; Habuchi, Satoshi ( 0000-0002-6663-2807 ) ; Kusakabe, Takahiro; Merzaban, Jasmeen S. ( 0000-0002-7276-2907 )
Abstract:
Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Conference/Event name:
Winter Enrichment Program 2017 - Poster Competition
Issue Date:
8-Jan-2017
Type:
Poster
Appears in Collections:
Posters; Winter Enrichment Program 2017

Full metadata record

DC FieldValue Language
dc.contributor.authorAleisa, Fajr Aen
dc.contributor.authorSakashita, Kosukeen
dc.contributor.authorLee, Jaemanen
dc.contributor.authorAbu Samra, Dina Bashir Kamilen
dc.contributor.authorHabuchi, Satoshien
dc.contributor.authorKusakabe, Takahiroen
dc.contributor.authorMerzaban, Jasmeen S.en
dc.date.accessioned2017-05-07T05:47:58Z-
dc.date.available2017-05-07T05:47:58Z-
dc.date.issued2017-01-08-
dc.identifier.urihttp://hdl.handle.net/10754/623363-
dc.description.abstractSelectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.en
dc.titleShort consensus repeat domains extend the E-selectin structure in order to grab cells out of flowen
dc.typePosteren
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.conference.dateJanuary 8-21 2017en
dc.conference.nameWinter Enrichment Program 2017 - Poster Competitionen
dc.conference.locationKAUSTen
dc.contributor.institutionKyushu University, Fukuoka, Japanen
kaust.authorAleisa, Fajr Aen
kaust.authorSakashita, Kosukeen
kaust.authorLee, Jaemanen
kaust.authorAbu Samra, Dina Bashir Kamilen
kaust.authorHabuchi, Satoshien
kaust.authorMerzaban, Jasmeen S.en
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.