Multiple low-affinity interactions support binding of human osteopontin to integrin α X β 2

Kläning, Eva; Christensen, Brian; Bajic, Goran; Hoffmann, Søren Vrønning; Jones, Nykola C.; Callesen, Morten M.; Andersen, Gregers Rom; Sørensen, Esben S.; Vorup-Jensen, Thomas

doi:10.1016/j.bbapap.2015.03.008

Cited by 13 publications

(16 citation statements)

References 56 publications

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“…Next to the RGD motif is the serine-valine-valine-typrosine-glycine-leucine-arginine (SVVYGLR) sequence in humans or serine-leucine-alanine-tyrosine-glycine-leucine-arginine (SLAYGLR) sequence in mice and rats, which is exposed upon cleavage with thrombin and interacts with α 4 β 1 , α 9 β 1 , α 4 β 7 integrins 18-20. Additionally, another integrin α x β 2 , which is neither RGD nor SVVYGLR dependent, has been reported to mediate the effects of OPN 21, 22. In addition to interacting with integrins, OPN has also been reported to bind to the spliced variant forms of CD44, notably v6 and v7, but the specific binding domain in OPN remains elusive 23.…”

Section: The Structure Of Opn and Its Receptorsmentioning

confidence: 99%

Role of Osteopontin in Liver Diseases

et al. 2016

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Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases.

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Section: The Structure Of Opn and Its Receptorsmentioning

confidence: 99%

Role of Osteopontin in Liver Diseases

et al. 2016

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“…However, there is no distinct and official benchmark for percentage recovery to be achieved in a quantitative analysis. The AOAC guidelines suggest that the lower the concentration of analyte in the sample, the bigger the tolerance [13]. The guidelines further indicate the recovery rate as 92-105%, 90-108% and 85-110% for analyte at concentrations of 1, 0.1 and 0.01%, respectively.…”

Section: Precision and Accuracymentioning

confidence: 99%

“…In particular, reversed-phase high-performance liquid chromatography (RP-HPLC) is a common analytical method that has been widely used. Previously, liquid chromatography and mass spectrometry were applied to measure human OPN only as a biomarker [9], for identification and characterization of bovine OPN fragments [10,11] and to separate N-and C-terminal in investigating the binding of human OPN to integrin [12,13] as summarized in Table 1 (Section 3.1).…”

Section: Introductionmentioning

confidence: 99%

A Reversed-Phase HPLC Method for Determination of Osteopontin in Infant Formula

Wazed

Farid

2019

Applied Sciences

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Osteopontin (OPN) is a multifunctional whey protein which has recently received much attention for possibly applications in fortifying infant milk formula (IMF) with its bioactivity. However, to date, there is no established high-performance liquid chromatography (HPLC) method to quantify this protein in milk or IMF. In this study, a rapid, simple, isocratic and reliable reversed-phase HPLC method was developed and validated to quantify the OPN in IMF. A C18 column (4.6 × 150 mm × 5 micron) was employed with 20% of 0.1% trifluoroacetic acid (TFA) and 80% of 60% acetonitrile in 0.1% TFA for 10 min detected at 214 nm. The flow rate was 0.3 mL/min with an injection volume of 10 µL. The column temperature was 40 °C, and the peak appeared after 4 min. The validation was based on the system suitability, linearity (r2 = 0.999), limit of detection (LOD) (0.14 mg/L), limit of quantitation (LOQ) (0.41 mg/L), precision (% relative standard deviation (RSD) < 0.2), recovery (% RSD < 3) and robustness. The results confirm that the method developed is suitable for OPN determination in IMF.

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“…The function of OPN is highly reliant on tissue-specific posttranslational processing (see for example (15,16)), including phosphorylation by the Golgi FAM20C (17,18) and other kinases, N-and O-glycosylation (4), and proteolysis (19). A variety of structural methods, including nuclear magnetic resonance (NMR) spectroscopy, synchrotron radiation circular dichroism, and small-angle x-ray scattering (SAXS), have been deployed to study various osteopontin peptides (20)(21)(22)(23)(24).…”

Section: Osteopontin and Biomineralizationmentioning

confidence: 99%

Effect of Phosphorylation on a Human-like Osteopontin Peptide

Lenton

Grimaldo

Roosen-Runge

et al. 2017

Biophysical Journal

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The last decade established that the dynamic properties of the phosphoproteome are central to function and its modulation. The temporal dimension of phosphorylation effects remains nonetheless poorly understood, particularly for intrinsically disordered proteins. Osteopontin, selected for this study due to its key role in biomineralization, is expressed in many species and tissues to play a range of distinct roles. A notable property of highly phosphorylated isoforms of osteopontin is their ability to sequester nanoclusters of calcium phosphate to form a core-shell structure, in a fluid that is supersaturated but stable. In Biology, this process enables soft and hard tissues to coexist in the same organism with relative ease. Here, we extend our understanding of the effect of phosphorylation on a disordered protein, the recombinant human-like osteopontin rOPN. The solution structures of the phosphorylated and unphosphorylated rOPN were investigated by small-angle x-ray scattering and no significant changes were detected on the radius of gyration or maximum interatomic distance. The picosecond-to-nanosecond dynamics of the hydrated powders of the two rOPN forms were further compared by elastic and quasi-elastic incoherent neutron scattering. Phosphorylation was found to block some nanosecond side-chain motions while increasing the flexibility of other side chains on the faster timescale. Phosphorylation can thus selectively change the dynamic behavior of even a highly disordered protein such as osteopontin. Through such an effect on rOPN, phosphorylation can direct allosteric mechanisms, interactions with substrates, cofactors and, in this case, amorphous or crystalline biominerals.

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Multiple low-affinity interactions support binding of human osteopontin to integrin α X β 2

Cited by 13 publications

References 56 publications

Role of Osteopontin in Liver Diseases

Role of Osteopontin in Liver Diseases

A Reversed-Phase HPLC Method for Determination of Osteopontin in Infant Formula

Effect of Phosphorylation on a Human-like Osteopontin Peptide

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