Integrin and Selectin Structure

Integrin and Selectin StructureDaniel ZhangIntegrinLAD I- Firm Adhesion

IntroductionHeterodimer and subunitsI and I domainsNon-covalently associatedFunctional heterodimeric receptorsClassified according to subunit composition and ligand binding characteristicsBARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280.

SubunitI domainLigand bindingMg2+ coordinatedMetal-ion-dependent adhesion site (MIDAS)7-bladed -propeller3 or 4 blades contain EF-hand domainsAllows Ca2+ bindingAllosterically affects ligand bindingThighCalf-1, 2 domainsForming leg

BARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280. SubunitI domainLigand bindingMg2+ coordinated (MIDAS)Adjacent to MIDAS (ADMIDAS): Ca2+ inhibition/Mn2+ activationHybrid domainPlexin-sempahorin-integrin (PSI) domain4 cysteine-rich epidermal growth factors (EGF)

BARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280.

ICAM-1, -2: Targets

GAHMBERG, C. G. 1997. Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules. Current opinion in cell biology, 9, 643-650.ICAM-1, -2: Targets

RUOSLAHTI, E. 1991. Integrins. The Journal of Clinical Investigation, 87, 1-5.Diversity

BARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280.DiversityVertebrates: 18 alpha subunits, 8 beta subunits, 24 possible heterodimersIntegrins classified according to ligand binding characteristics or subunit composition1, 2, v containing integrins largest groups

BARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280.MutationsOccurs in the 2 integrin subfamily: ITGB2 geneNumerous observed mutations, case-to-caseNucleotide deletionsAbnormal splicing defectsPoint mutation, defective initiation codonmissense- single amino acidPSI domainCysteine rich regionSelectinLAD II- Rolling Adhesion

Named after cells on which first discovered, but present on multitude of cellsMCEVER, R. P. 1994. Selectins. Current Opinion in Immunology, 6, 75-84.

Signalling peptideLectin domain- sugar bindingDirect mediation of cell cell contact via membrane surface carbohydratesEGF- like motifSupports optimal ligand recognitionModulates conformation of lectin domainConcensus repeatsTransmembrane domainCytoplasmic tail

MCEVER, R. P. 1994. Selectins. Current Opinion in Immunology, 6, 75-84.TargetsCarbohydrates expressed on cell surfaceThree general categoriesOligosaccharides related to sialyl-Lewis x; sialyl-Lewis aPhosphorylated mono and polysaccharidesSulfated polysaccharides Oligosaccharides most studied

Targets

terminal residues of larger oligosaccharides on glycoproteins/glycolipidsNote fucose on top

BEVILACQUA, M. P. & NELSON, R. M. 1993. Selectins. The American Society for Clinical Investigation, 91, 379-387.DefectsInability to fucosylate oligosaccharides Defect in GDP-fucose transporter SLC35C1Selectin does not recognize/bind to ligand

ReferencesBARCZYK, M., GULLBERG, D. & CARRACEDO, S. 2010. Integrins. Cell and Tissue Research, 269280.BEVILACQUA, M. P. & NELSON, R. M. 1993. Selectins. The American Society for Clinical Investigation, 91, 379-387.ETZIONI, A. & TONETTI, M. 2000. Leukocyte adhesion deficiency II from A to almost Z. Immunological Reviews, 178, 138-147.GAHMBERG, C. G. 1997. Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules. Current opinion in cell biology, 9, 643-650.HARRIS, E. S., WEYRICH, A. S. & ZIMMERMAN, G. A. 2013. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Current Opinion in Hematology, 20, 16-25.MCEVER, R. P. 1994. Selectins. Current Opinion in Immunology, 6, 75-84.RUOSLAHTI, E. 1991. Integrins. The Journal of Clinical Investigation, 87, 1-5.