A Cluster of Basic Amino Acid Residues in the γ370−381 Sequence of Fibrinogen Comprises a Binding Site for Platelet Integrin αIIbβ3(Glycoprotein IIb/IIIa)

Podolnikova, Nataly P.; Gorkun, Oleg V.; Loreth, R. M.; Yee, Vivien C.; Lord, Susan T.; Ugarova, Tatiana P.

doi:10.1021/bi051581d

Cited by 34 publications

(40 citation statements)

References 58 publications

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“…Intriguingly, the structure of the ␥C domain (32) reveals two pairs of basic residues on exposed surfaces of the protein that are crucial for the interaction with the integrin. In particular, substitution of either Lys 380 or Lys 381 of ␥C peptides with alanine reduces peptide binding to ␣IIb␤3, and a double substitution completely abolishes binding (43). The data from other systems are completely consistent with our data showing loss of binding and activity of CD23-derived peptides when Arg 172 and Lys 173 are substituted with alanine.…”

Section: Discussionsupporting

confidence: 90%

“…The ␣v␤5 integrin recognizes the HIV Tat protein via a non-RGD motif that is basic in character (25). Studies of binding of ␣IIb␤3 to peptide fragments of fibrinogen demonstrated that the integrin recognizes a cluster of basic residues located between residues 370 and 381 of the ␥C domain that is devoid of an RGD sequence (43). Intriguingly, the structure of the ␥C domain (32) reveals two pairs of basic residues on exposed surfaces of the protein that are crucial for the interaction with the integrin.…”

Section: Discussionmentioning

confidence: 99%

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αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

Borland

Edkins

Acharya

et al. 2007

Journal of Biological Chemistry

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CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells that has biological activity in both membrane-bound and freely soluble forms, acting via a number of receptors, including integrins. We demonstrate here that soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD-independent interaction with the ␣v␤5 integrin. The integrin recognizes a tripeptide motif in a small disulfidebonded loop at the N terminus of the lectin head region of CD23, centered around Arg 172 , Lys 173 , and Cys 174 (RKC). This RKC motif is present in all forms of sCD23 with cytokine-like activity, and cytokine activity is independent of the lectin head, an "inverse RGD" motif, and the CD21 and IgE binding sites. RKCcontaining peptides derived from this region of CD23 bind ␣v␤5 and are biologically active. The binding and activity of these peptides is unaffected by inclusion of a short peptide containing the classic RGD sequence recognized by integrins, and, in farWestern analyses, RKC-containing peptides bind to the ␤ subunit of the ␣v␤5 integrin. The interaction between ␣v␤5 and sCD23 indicates that integrins deliver to cells important signals initiated by soluble ligands without the requirement for interactions with RGD motifs in their common ligands. This mode of integrin signaling may not be restricted to ␣v␤5.CD23 is a 45-kDa type II transmembrane glycoprotein that functions as the low affinity receptor for IgE and negatively regulates IgE production by B lymphocytes (1-5). CD23 is cleaved by membrane-associated metalloproteases (6, 7) to yield soluble CD23 (sCD23) 6 proteins with molecular masses ranging from 37 to 16 kDa, all of which retain the capacity to regulate IgE synthesis; human sCD23 proteins exhibit pleiotropic cytokine-like activities (1-3). In the B cell compartment, sCD23 inhibits apoptosis of germinal center centrocytes and promotes their differentiation into plasmablasts (8), at least in part by binding to CD21 (9), and sCD23 also inhibits apoptosis in pre-B cell lines (10) through, as we report here, an interaction with the ␣v␤5 integrin. In association with interleukin-1␣, sCD23 promotes differentiation of monocytes and early thymocyte precursors (11) and, via binding to the ␣M␤2 (CD11b-CD18), ␣X␤2 (CD11c-CD18) (12), and ␣v␤3 integrins (13), stimulates tumor necrosis factor-␣ and interleukin-1␣ production by monocytes. The structures of the derCD23 protein, a naturally occurring sCD23 fragment generated by action of the derp1 protease from Dermatophagoides pteronyssinus, and of a 25-kDa sCD23 (residues 150 -321), have recently been solved by heteronuclear nuclear magnetic resonance spectroscopy (14) and x-ray crystallography (15), respectively. Although there are pronounced differences between the structures derived by the two methods, both show a generally consistent overall structure for the C-type lectin head domain comprising eight ␤ sheets and two ␣ helices (14, 15). The NMR structure reveals a striking distribution of acidic and basic residues on opposites faces of t...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

Borland

Edkins

Acharya

et al. 2007

Journal of Biological Chemistry

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“…Thus, platelet spreading on surfaces coated with fibrin lacking ␤ chain residues 15-42 is substantially impaired (22). Further, antibodies against the ␥316 -322 region inhibit clot retraction (23), and a site designated P3 at ␥370 -383 has been identified that also mediates fibrin clot retraction and binds ␣IIb␤3 (25,26). Mutational analyses have confirmed that both ␥408 -411 AGDV and P3 are required for the full adhesive activity of fibrin for platelets.…”

Section: Discussionmentioning

confidence: 99%

“…These observations suggest that a site or sites in addition to the RGD and C-terminal ␥ chain motifs participate in the interaction of platelets with fibrin during thrombus growth and clot contraction. Candidate sites proposed previously include residues 15-42 in the ␤ chain (22), as well as residues 316 -322 (23,24) and 370 -381 (25,26) in the ␥ chain ( Fig. 1).…”

mentioning

confidence: 95%

The Platelet Integrin αIIbβ3 Differentially Interacts with Fibrin Versus Fibrinogen

Litvinov

Farrell

Weisel

et al. 2016

Journal of Biological Chemistry

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Fibrinogen binding to the integrin ␣IIb␤3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However, in vivo ␣IIb␤3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogen versus fibrin to ␣IIb␤3-mediated platelet functions are unknown. Here, we compared the interaction of ␣IIb␤3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified ␣IIb␤3. When ␣IIb␤3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with ␣IIb␤3 and a greater binding strength. ␣IIb␤3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen-and fibrin-␣IIb␤3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants ␣D97E or ␣D574E with mutated RGD motifs. Fibrin made from a fibrinogen ␥/␥ variant lacking the ␥C ␣IIb␤3-binding motif was more reactive with ␣IIb␤3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with ␣IIb␤3 than fibrinogen. Fibrin is also less sensitive to ␣IIb␤3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of ␣IIb␤3 binding activity in the absence of the ␥C-dodecapeptide and the ␣-chain RGD sequences suggests that the ␣IIb␤3-binding sites in fibrin are not confined to its known ␥-chain and RGD motifs.

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“…23,24 The membrane-bound peptides were tested for their ability to bind the a M I-domain according to a procedure described earlier. 23 In brief, the membrane was blocked with 1% BSA and then incubated with 10 mg/mL of 125 I-labeled a M I-domain in Tris-buffered saline containing 1 mM MgCl 2 .…”

Section: Synthesis Of Cellulose-bound Peptide Librariesmentioning

confidence: 99%

Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin αMβ2 (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

Lishko¹,

Moreno²,

Podolnikova³

et al. 2016

RRBC

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A Cluster of Basic Amino Acid Residues in the γ370−381 Sequence of Fibrinogen Comprises a Binding Site for Platelet Integrin α_IIbβ₃(Glycoprotein IIb/IIIa)

Cited by 34 publications

References 58 publications

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

The Platelet Integrin αIIbβ3 Differentially Interacts with Fibrin Versus Fibrinogen

Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin α<sub>M</sub>β<sub>2</sub> (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

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A Cluster of Basic Amino Acid Residues in the γ370−381 Sequence of Fibrinogen Comprises a Binding Site for Platelet Integrin αIIbβ3(Glycoprotein IIb/IIIa)

Cited by 34 publications

References 58 publications

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

The Platelet Integrin αIIbβ3 Differentially Interacts with Fibrin Versus Fibrinogen

Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin &alpha;<sub>M</sub>&beta;<sub>2</sub> (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

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Resources

About

A Cluster of Basic Amino Acid Residues in the γ370−381 Sequence of Fibrinogen Comprises a Binding Site for Platelet Integrin α_IIbβ₃(Glycoprotein IIb/IIIa)

Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin α<sub>M</sub>β<sub>2</sub> (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria