Mapping the binding domains of the αIIb subunit

A study performed on the activated form of the platelet integrin α IIbβ3

Nikolaos Biris, Morfis Abatzis, John V. Mitsios, Maria Sakarellos-Daitsiotis, Constantinos Sakarellos, Demokritos Tsoukatos, Alexandros D. Tselepis, Lambros Michalis, Dimitrios Sideris, Georgia Konidou, Ketty Soteriadou, Vassilios Tsikaris

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

αIIbβ3, a member of the integrin family of adhesive protein receptors, is the most abundant glycoprotein on platelet plasma-membranes and binds to adhesive proteins via the recognition of short amino acid sequences, for example the ubiquitous RGD motif. However, elucidation of the ligand-binding domains of the receptor remains controversial, mainly owing to the fact that integrins are conformationally labile during purification and storage. In this study, a detailed mapping of the extracellular region of the αIIb subunit is presented, using overlapping 20-peptides, in order to identify the binding sites of α IIb potentially involved in the platelet-aggregation event. Regions αIIb 313-332, αIIb 265-284 and α IIb 57-64 of αIIbβ3 were identified as putative fibrinogen-binding domains because the corresponding peptides inhibited platelet aggregation and antagonized fibrinogen association, possibly by interacting with this ligand. The latter is further supported by the finding that the above peptides did not interfere with the binding of PAC-1 to the activated form of αIIbβ3. Furthermore, αIIb313-332 was found to bind to fibrinogen in a solid-phase binding assay. It should be emphasized that all the experiments in this study were carried out on activated platelets and consequently on the activated form of this integrin receptor. We hypothesize that RAD and RAE adhesive motifs, encompassed in αIIb 313-332, 265-284 and 57-64, are capable of recognizing complementary domains of fibrinogen, thus inhibiting the binding of this ligand to platelets.

Original languageEnglish (US)
Pages (from-to)3760-3767
Number of pages8
JournalEuropean Journal of Biochemistry
Volume270
Issue number18
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Platelets
Integrins
Fibrinogen
Blood Platelets
Adhesives
Ligands
Platelet Aggregation
Peptides
Platelet Membrane Glycoproteins
Agglomeration
Amino Acid Sequence
Cell membranes
Proteins
Binding Sites
Cell Membrane
Purification
Assays
Glycoproteins
Association reactions
Amino Acids

Keywords

  • α mapping
  • αβ receptor
  • α-binding domains
  • Integrin inhibitors
  • Platelet-aggregation inhibitors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Biris, N., Abatzis, M., Mitsios, J. V., Sakarellos-Daitsiotis, M., Sakarellos, C., Tsoukatos, D., ... Tsikaris, V. (2003). Mapping the binding domains of the αIIb subunit: A study performed on the activated form of the platelet integrin α IIbβ3. European Journal of Biochemistry, 270(18), 3760-3767. https://doi.org/10.1046/j.1432-1033.2003.03762.x

Mapping the binding domains of the αIIb subunit : A study performed on the activated form of the platelet integrin α IIbβ3. / Biris, Nikolaos; Abatzis, Morfis; Mitsios, John V.; Sakarellos-Daitsiotis, Maria; Sakarellos, Constantinos; Tsoukatos, Demokritos; Tselepis, Alexandros D.; Michalis, Lambros; Sideris, Dimitrios; Konidou, Georgia; Soteriadou, Ketty; Tsikaris, Vassilios.

In: European Journal of Biochemistry, Vol. 270, No. 18, 09.2003, p. 3760-3767.

Research output: Contribution to journalArticle

Biris, N, Abatzis, M, Mitsios, JV, Sakarellos-Daitsiotis, M, Sakarellos, C, Tsoukatos, D, Tselepis, AD, Michalis, L, Sideris, D, Konidou, G, Soteriadou, K & Tsikaris, V 2003, 'Mapping the binding domains of the αIIb subunit: A study performed on the activated form of the platelet integrin α IIbβ3', European Journal of Biochemistry, vol. 270, no. 18, pp. 3760-3767. https://doi.org/10.1046/j.1432-1033.2003.03762.x
Biris, Nikolaos ; Abatzis, Morfis ; Mitsios, John V. ; Sakarellos-Daitsiotis, Maria ; Sakarellos, Constantinos ; Tsoukatos, Demokritos ; Tselepis, Alexandros D. ; Michalis, Lambros ; Sideris, Dimitrios ; Konidou, Georgia ; Soteriadou, Ketty ; Tsikaris, Vassilios. / Mapping the binding domains of the αIIb subunit : A study performed on the activated form of the platelet integrin α IIbβ3. In: European Journal of Biochemistry. 2003 ; Vol. 270, No. 18. pp. 3760-3767.
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AU - Sakarellos-Daitsiotis, Maria

AU - Sakarellos, Constantinos

AU - Tsoukatos, Demokritos

AU - Tselepis, Alexandros D.

AU - Michalis, Lambros

AU - Sideris, Dimitrios

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