Platelet adhesion to cyanogen-bromide fragments of collagen alpha 1(I) under flow conditions

Saelman, EU; Horton, LF; Barnes, M.J.; Gralnick, HR; Hese, KM; Nieuwenhuis, H. K.; Groot, PG de; Sixma, JJ

doi:10.1182/blood.v82.10.3029.bloodjournal82103029

Cited by 7 publications

(10 citation statements)

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“…Cell adhesion to native (triple-helical) collagen type IV involving integrin al,c1 is mediated by a single site encompassing an Asp residue at position 461 in the acl (IV) chain and an Arg residue at the identical position in the a2(IV) chain [4]. The integrin collagen receptor a2fl1 is thought to play an important role in the interaction of collagen with platelets [5][6][7][8][9][10][11][12][13]. Interaction between integrin a2,f1…”

Section: Methodsmentioning

confidence: 99%

Integrin α2β1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity

Morton¹,

Hargreaves

Farndale

et al. 1995

Biochemical Journal

306

238

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The platelet reactivities of two simple collagen-like synthetic peptides, Gly-Lys-Hyp-(Gly-Pro-Hyp)10-Gly-Lys-Hyp-Gly and Gly-Cys-Hyp-(Gly-Pro-Hyp)10-Gly-Cys-Hyp-Gly, were investigated. Both peptides adopted a stable triple-helical conformation in solution. Following cross-linking, both peptides proved to be highly platelet-aggregatory, more active than collagen fibres, inducing aggregation at concentrations as low as 20 ng/ml. These peptides formed microaggregates in solution, and cross-linking was thought to stabilize these structures, allowing expression of their platelet reactivity at 37 degrees C. Like collagen fibres, the peptides caused platelet secretion and release of arachidonate from platelet membrane lipids as well as activation of integrin alpha IIb beta 3 culminating in aggregation. Monoclonal antibodies directed against the integrin alpha 2 beta 1 failed to prevent aggregation release of arachidonate or platelet adhesion to the peptides. Our results indicate that collagen can activate platelets by a mechanism that is independent of integrin alpha 2 beta 1 and for which collagen tertiary and quaternary structures are sufficient alone for activity without the involvement of highly specific cell-recognition sequences.

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Section: Methodsmentioning

confidence: 99%

Integrin α2β1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity

Morton¹,

Hargreaves

Farndale

et al. 1995

Biochemical Journal

306

238

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“…However, alignments of the isolated peptides with the amino acid sequence of the α1(I) chain from human type I collagen revealed a number of matches of differing levels of homology. These sites were distributed throughout the sequence, and included sites in CB fragments 2, 3, 4, 6, 7 and 8 [40]. Most sites were characterized by one or more gaps of different lengths and low level identities in the range 12-25 %.…”

Section: Table 1 Inhibition Of Mmp-2 Cbd and Mmp-8 Activities In The mentioning

confidence: 99%

Inhibition of MMP-2 gelatinolysis by targeting exodomain–substrate interactions

Chen

Wang

et al. 2007

Biochemical Journal

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MMP-2 (matrix metalloproteinase 2) contains a CBD (collagen-binding domain), which is essential for positioning gelatin substrate molecules relative to the catalytic site for cleavage. Deletion of the CBD or disruption of CBD-mediated gelatin binding inhibits gelatinolysis by MMP-2. To identify CBD-binding sites on type I collagen and collagen peptides with the capacity to compete CBD binding of gelatin and thereby inhibit gelatinolysis by MMP-2, we screened a one-bead one-peptide combinatorial peptide library with recombinant CBD as bait. Analyses of sequences from the CBD-binding peptides pointed to residues 715-721 in human alpha1(I) collagen chain as a binding site for CBD. A peptide (P713) including this collagen segment was synthesized for analyses. In SPR (surface plasmon resonance) assays, the CBD and MMP-2(E404A), a catalytically inactive MMP-2 mutant, both bound immobilized P713 in a concentration-dependent manner, but not a scrambled control peptide. Furthermore, P713 competed gelatin binding by the CBD and MMP-2(E404A). In control assays, neither of the non-collagen binding alkylated CBD or MMP-2 with deletion of CBD (MMP-2DeltaCBD) bound P713. Consistent with the exodomain functions of the CBD, P713 inhibited approximately 90% of the MMP-2 gelatin cleavage, but less than 20% of the MMP-2 activity on a peptide substrate (NFF-1) which does not require the CBD for cleavage. Confirming the specificity of the inhibition, P713 did not alter MMP-2DeltaCBD or MMP-8 activities. These experiments identified a CBD-binding site on type I collagen and demonstrated that a corresponding synthetic peptide can inhibit hydrolysis of type I and IV collagens by competing CBD-mediated gelatin binding to MMP-2.

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“…The non-uniform distribution of integrin ␣2␤1 recognition sites among triple-helical peptides of collagens I and III produced by cyanogen bromide fragmentation (CB peptides) [35][36][37] supported a mapping approach using synthetic peptides. These comprised overlapping stretches of the collagen (guest) sequence under test flanked by GPP or GPO (host) polymers [9].…”

Section: Recognition Of Integrin ␣2␤1mentioning

confidence: 99%

Collagen-platelet interactions: recognition and signalling

Farndale

Siljander

Onley

et al. 2003

Biochemical Society Symposia

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The collagen-platelet interaction is central to haemostasis and may be a critical determinant of arterial thrombosis, where subendothelium is exposed after rupture of atherosclerotic plaque. Recent research has capitalized on the cloning of an important signalling receptor for collagen, glycoprotein VI, which is expressed only on platelets, and on the use of collagen-mimetic peptides as specific tools for both glycoprotein VI and integrin α2ϐ1. We have identified sequences, GPO and GFOGER (where O denotes hydroxyproline), within collagen that are recognized by the collagen receptors glycoprotein VI and integrin α2ϐ1 respectively, allowing their signalling properties and specific functional roles to be examined. Triple-helical peptides containing these sequences were used to show the signalling potential of integrin α2ϐ1, and to confirm its important contribution to platelet adhesion. Glycoprotein VI appears to operate functionally on the platelet surface as a dimer, which recognizes GPO motifs that are separated by four triplets of collagen sequence. These advances will allow the relationship between the structure of collagen and its haemostatic activity to be established.

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Platelet adhesion to cyanogen-bromide fragments of collagen alpha 1(I) under flow conditions

Cited by 7 publications

References 0 publications

Integrin α2β1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity

Integrin α2β1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity

Inhibition of MMP-2 gelatinolysis by targeting exodomain–substrate interactions

Collagen-platelet interactions: recognition and signalling

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