Platelet glycoprotein VI: its structure and function

Moroi, Masaaki; Jung, Stéphanie

doi:10.1016/j.thromres.2004.06.046

Cited by 189 publications

(165 citation statements)

References 79 publications

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“…A comparison of the individual domains of OSCAR with structures deposited in the Protein Data Bank (PDB) using the DALI server revealed that the D1 and D2 domains of OSCAR share the closest structural similarity to ILT3 domain 1 and ILT2 domain 4, respectively (Z-score 15.2 and 10.4 and rmsd 1.7 and 2.2 over 94 and 98 amino acids, respectively) (22). Interestingly, the OSCAR D1 domain does not display a 3 10 helical region in the C′ region or in the FG-loop, as found in some of the MHC-binding members of the LRC (23). Instead the region shows a prominent CC′-loop from P71 to P76 that is brought closer to the opposing FG-loop than in other members.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, receptor activator of nuclear factor-κB ligand (RANKL) differentiation of monocytes to osteoclasts is increased in the presence of collagen-like peptides (CLPs) and can be inhibited by the addition of OSCAR antibodies (9). The description of OSCAR as a collagen-binding receptor of the LRC family places OSCAR with other collagenbinding proteins of this family, including glycoprotein VI (GPVI), leukocyte-associated Ig-like receptor-1 (LAIR-1), and the putative member LILRB4 (9)(10)(11)(12)(13)(14)(15)(16).…”

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confidence: 99%

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Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors

Haywood

Chen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Human osteoclast-associated receptor (OSCAR) is an immunoglobulin (Ig)-like collagen receptor that is up-regulated on osteoclasts during osteoclastogenesis and is expressed in a range of myeloid cells. As a member of the leukocyte receptor complex family of proteins, OSCAR shares a high degree of sequence and structural homology with other collagen receptors of this family, including glycoprotein VI, leukocyte-associated Ig-like receptor-1, and leukocyte Ig-like receptor B4, but recognizes a unique collagen sequence. Here, we present the crystal structures of OSCAR in its free form and in complex with a triple-helical collagen-like peptide (CLP). These structures reveal that the CLP peptide binds only one of the two Ig-like domains, the membrane-proximal domain (domain 2) of OSCAR, with the middle and trailing chain burying a total of 661 Å 2 of solvent-accessible collagen surface. This binding mode is facilitated by the unusual topography of the OSCAR protein, which displays an obtuse interdomain angle and a rotation of domain 2 relative to the membrane-distal domain 1. Moreover, the binding of the CLP to OSCAR appears to be mediated largely by tyrosine residues and conformational changes at a shallow Phe pocket. Furthermore, we investigated CLP peptides as inhibitors of osteoclastogenesis and found that a peptide length of 40 amino acids is required to ensure adequate inhibition of osteoclastogenesis in vitro. These findings provide valuable structural insights into the mode of collagen recognition by OSCAR and into the use of synthetic peptide matrikines for osteoclastogenesis inhibition.C ollagen is a highly versatile family of proteins consisting of more than 28 members that achieve a high degree of complexity through association of different collagen types, the use of multiple transcription initiation sites, alternative splicing patterns, posttranslational modifications, and a wide range of expression patterns (1). Despite this heterogeneity, studies of collagen over the past 60 y have revealed that collagens are commonly found as large fibrillar structures consisting of varying lengths of righthanded triple-helical structures that are formed by association of three left-handed polyproline type II helices with a one-residue stagger (2, 3). Crucial to the formation of these triple helical structures are the repetitive amino acid triplet sequences G-X-Y, of which the most frequently observed triplet is G-P-O, with O representing 4-hydroxyproline (4). In these structures the obligate glycine of the triplet is buried toward the center of the helix and is solvent inaccessible, whereas the X and Y residues are solvent accessible with the latter providing crucial stability to collagen fibrils through interchain hydrogen bonding (3). The diversity of imino and amino acids within these X and Y repetitive sequences are thought to result in changes in the helical parameters of collagen, which vary from a tight left-handed 7 2 to a looser 10 3 helical symmetry, and could provide a more flexible and accessible motif fo...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors

Haywood

Chen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Plateletspecific glycoprotein VI (GPVI) is a major factor in the initiation of platelet aggregation through binding to these collagens (14). It has been demonstrated that GPVI binds to repeated (GlyProHyp) n collagen sequences (15).…”

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confidence: 99%

Biological role of prolyl 3-hydroxylation in type IV collagen

Pokidysheva

Boudko

Vranka

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Collagens constitute nearly 30% of all proteins in our body. Type IV collagen is a major and crucial component of basement membranes. Collagen chains undergo several posttranslational modifications that are indispensable for proper collagen function. One of these modifications, prolyl 3-hydroxylation, is accomplished by a family of prolyl 3-hydroxylases (P3H1, P3H2, and P3H3). The present study shows that P3H2-null mice are embryonic-lethal by embryonic day 8.5. The mechanism of the unexpectedly early lethality involves the interaction of non-3-hydroxylated embryonic type IV collagen with the maternal platelet-specific glycoprotein VI (GPVI). This interaction results in maternal platelet aggregation, thrombosis of the maternal blood, and death of the embryo. The phenotype is completely rescued by producing double KOs of P3H2 and GPVI. Double nulls are viable and fertile. Under normal conditions, subendothelial collagens bear the GPVI-binding sites that initiate platelet aggregation upon blood exposure during injuries. In type IV collagen, these sites are normally 3-hydroxylated. Thus, prolyl 3-hydroxylation of type IV collagen has an important function preventing maternal platelet aggregation in response to the early developing embryo. A unique link between blood coagulation and the ECM is established. The newly described mechanism may elucidate some unexplained fetal losses in humans, where thrombosis is often observed at the maternal/fetal interface. Moreover, epigenetic silencing of P3H2 in breast cancers implies that the interaction between GPVI and non-3-hydroxylated type IV collagen might also play a role in the progression of malignant tumors and metastasis.C ollagens constitute nearly 30% of all proteins in our body (1).Among the 29 collagen types, type IV collagen is a major and crucial component of basement membranes (2). Different collagen types assemble into different structures. Examples of these structures are fibrils (collagen types I, II, and III) and networks (collagen types IV and VI) (1). Proper posttranslational modifications of collagen chains are critical for ultimate quaternary structure formation and function. Posttranslational modifications of collagen include prolyl 4-hydroxylation, lysyl hydroxylation and glycosylation, and prolyl 3-hydroxylation (3). The prolyl 3-hydroxylase family (P3H1, P3H2, and P3H3) is responsible for the process of prolyl 3-hydroxylation. These enzymes modify specific prolines in GlyProHyp [Hyp is 4(R)-hydroxyproline] sequences into 3(S)-hydroxyproline (3Hyp) (4). Although prolyl 4-hydroxylation occurs at almost every Yaa position proline in the Gly-Xaa-Yaa repeated sequence of collagen, prolyl 3-hydroxylation happens only at a few specific Xaa position prolines.P3H1 is the main enzyme modifying type I collagen. Mutations in P3H1 have been found to cause severe osteogenesis imperfecta (OI) in both humans and mice (5, 6). The causative molecular mechanism of the OI phenotype remains speculative. Limited information is available about the substrate specificity of ...

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“…Platelets are activated by a diverse range of stimulators, leading to alterations in shape, adhesion, aggregation, and subsequent thrombus formation. Collagen is well-documented as a primary stimulator of human platelets (2,3). Platelets interact with collagen in subendothelium at the damaged site of the vessel wall.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, once subendothelium is exposed, platelets rapidly adhere to the exposed subendothelial collagen, which is characterized by the interaction of glycoprotein (GP) Ib/IX/V and von Willebrand factor (1), resulting in aggregation and hemostasis. GPVI and integrin α2β1 are the predominant collagen receptors located on the plasma membrane of platelets (2,3). GPVI forms a complex with the Fc receptor γ-chain (4,5).…”

Section: Introductionmentioning

confidence: 99%

AICAR reduces the collagen-stimulated secretion of PDGF-AB and release of soluble CD40 ligand from human platelets: Suppression of HSP27 phosphorylation via p44/p42 MAP kinase

Tsujimoto

Tokuda

Kuroyanagi

et al. 2016

Experimental and Therapeutic Medicine

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Abstract.We have previously reported that collagen-induced phosphorylation of heat shock protein (HSP) 27 via p44/p42 mitogen-activated protein (MAP) kinase in human platelets is sufficient to induce the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble cluster of differentiation 40 ligand (sCD40L). Adenosine monophosphate-activated protein kinase (AMPK), which is known to regulate energy homeostasis, has a crucial role as an energy sensor in various eukaryotic cells. The present study investigated the effects of 5-aminoimidazole-4-carbox amide-1-β-d-ribofuranosyl 5'-monophosphate (AICAR), which is an activator of AMPK, on the collagen-induced activation of human platelets. It was demonstrated that AICAR dose-dependently reduced collagen-stimulated platelet aggregation up to 1.0 µM. Analysis of the size of platelet aggregates demonstrated that AICAR decreased the ratio of large aggregates (50-70 µm), whereas the ratio of small aggregates (9-25 µm) was increased by AICAR administration. AICAR markedly attenuated the phosphorylation levels of p44/p42 MAP kinase and HSP27, which are induced by collagen.Furthermore, AICAR significantly decreased the secretion of PDGF-AB and the collagen-induced release of sCD40L. These results indicated that AICAR-activated AMPK may reduce the secretion of PDGF-AB and the collagen-induced release of sCD40L by inhibiting HSP27 phosphorylation via p44/p42 MAP kinase in human platelets.

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Platelet glycoprotein VI: its structure and function

Cited by 189 publications

References 79 publications

Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors

Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors

Biological role of prolyl 3-hydroxylation in type IV collagen

AICAR reduces the collagen-stimulated secretion of PDGF-AB and release of soluble CD40 ligand from human platelets: Suppression of HSP27 phosphorylation via p44/p42 MAP kinase

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