Palmitoylated peptide, being derived from the carboxyl-terminal sequence of the integrin Ξ±IIb cytoplasmic domain, inhibits talin binding to Ξ±IIbΞ²3

 
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2013 (EN)
Palmitoylated peptide, being derived from the carboxyl-terminal sequence of the integrin Ξ±IIb cytoplasmic domain, inhibits talin binding to Ξ±IIbΞ²3 (EN)

A. Gourogianni, (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας (EL)
A. Gourogianni, (EN)

The Ξ±IIb cytoplasmic domain of platelet integrin Ξ±IIbΞ²3 contains an unorganized acidic membrane-distal 1000LEEDDEEGE1008 region. We have shown that a platelet permeable peptide corresponding to the above region the palmitoyl-K-LEEDDEEGE (pal-K-1000-1008) inhibits platelet aggregation induced by thrombin or by pal-K-989-995, a palmitoylated peptide corresponding to the membrane-proximal Ξ±IIb cytoplasmic domain 989KVGFFKR995. We now tested the anti-aggregatory activity of (i) a lipid-modified scrambled acidic peptide (pal-K-GDDEELEEE), (ii) two smaller peptides derived from the acidic amino sequence: palmitoyl-K-1000LEEDDE1005 (pal-K-1000-1005) and palmitoyl-K-1005EEGE1008 (pal-K-1005-1008) and (iii) lipid-modified palmitoyl-acidic peptides with alanine (Ala) substitution at residues 1001, 1003, 1004 and 1005 and one peptide with a double Ala substitution at residues 1001 and 1004 of the 1000-1008 sequence. All the peptides tested showed an inhibitory activity, however, the palmitoylated peptide with the natural and the whole acidic sequence, being the most active. Our results suggest that the whole acidic sequence, rather than some specific amino acids, contributes to the aggregation inhibitory activity. The inhibitory peptide, pal-K-1000-1008, inhibited the association of talin with Ξ±IIbΞ²3 in thrombin-activated platelets, as demonstrated by co-immunoprecipitation experiments, while the scrambled peptide was inefficient. We suggest that, by interacting with Ξ±IIb cytoplasmic domain, pal-K-1000-1008 has an anti-aggregatory inhibitory activity due to a specific inhibition of talin binding to Ξ±IIbΞ²3. (EN)

Ξ±IIb-Cytoplasmic domain, integrin Ξ±IIbΞ²3, palmitoylated peptides, platelet aggregation inhibitors, talin (EN)

Πανεπιστήμιο Ιωαννίνων (EL)
University of Ioannina (EN)

Platelets (EN)

English

2013


Informa Plc. (EN)



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