Binding Mode Characterization of Osteopontin on Hydroxyapatite by Solution NMR Spectroscopy

Holzinger, Julian; Kotisch, Harald; Richter, Klaus W.; Konrat, Robert

doi:10.1002/cbic.202100139

Cited by 5 publications

(3 citation statements)

References 67 publications

(154 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although OPN exists in solution as an intrinsically disordered protein, it is hypothesized that binding to one or more of its partners induces a defined tertiary structure in the locality of the interaction that serves as the binding surface. This hypothesis has been confirmed by experiments in which structures of OPN bound to hydroxyapatite have been determined by NMR [ 47 , 48 ]. Thus, OPN may regulate the crystallization of calcium phosphate when hydroxyapatite is being laid down in bone formation.…”

Section: Opn Protein Structurementioning

confidence: 75%

Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

Leung

Myles

Morser

2023

Cancers

View full text Add to dashboard Cite

Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. Thrombin cleavage of OPN initiates OPN’s tumor-promoting activity, and thrombin cleavage fragments of OPN down-regulate the host immune anti-tumor response.

show abstract

Section: Opn Protein Structurementioning

confidence: 75%

Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

Leung

Myles

Morser

2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated such behaviors, with typical observations that phosphorylation expands neutral or negatively charged IDPs, and shrinks positively charged IDPs [28,61,68]. For example, a recent study used NMR to demonstrate that hyperphosphorylated osteopontin becomes extended, thereby preventing correct biomineralization of the bone mineral hydroxyapatite and causing dystrophic calcification [69]. However, a general principle remains difficult to extract due to the number of other parameters at play.…”

Section: Impacting the Chemistry And The Conformational Ensembles Of ...mentioning

confidence: 99%

How phosphorylation impacts intrinsically disordered proteins and their function

Newcombe

Delaforge

Hartmann‐Petersen

et al. 2022

Essays in Biochemistry

View full text Add to dashboard Cite

Phosphorylation is the most common post-translational modification (PTM) in eukaryotes, occurring particularly frequently in intrinsically disordered proteins (IDPs). These proteins are highly flexible and dynamic by nature. Thus, it is intriguing that the addition of a single phosphoryl group to a disordered chain can impact its function so dramatically. Furthermore, as many IDPs carry multiple phosphorylation sites, the number of possible states increases, enabling larger complexities and novel mechanisms. Although a chemically simple and well-understood process, the impact of phosphorylation on the conformational ensemble and molecular function of IDPs, not to mention biological output, is highly complex and diverse. Since the discovery of the first phosphorylation site in proteins 75 years ago, we have come to a much better understanding of how this PTM works, but with the diversity of IDPs and their capacity for carrying multiple phosphoryl groups, the complexity grows. In this Essay, we highlight some of the basic effects of IDP phosphorylation, allowing it to serve as starting point when embarking on studies into this topic. We further describe how recent complex cases of multisite phosphorylation of IDPs have been instrumental in widening our view on the effect of protein phosphorylation. Finally, we put forward perspectives on the phosphorylation of IDPs, both in relation to disease and in context of other PTMs; areas where deep insight remains to be uncovered.

show abstract

“…The analysis of OPN's amino acid residues reveals its robust binding ability to calcium ions, particularly on the crystal's (100) surface 15 – 17 . Studies modifying OPN's conformation through phosphorylation enhance its binding affinity to the HAP surface 18 – 21 . Amino acid residues containing carboxyl groups, like aspartic acid and glutamic acid, play a pivotal role in the interaction between proteins and crystals, as confirmed by molecular dynamics simulations of OPN adsorption 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

The impact of hydroxyapatite crystal structures and protein interactions on bone's mechanical properties

Sun,

Wang,

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Hydroxyapatite (HAP) constitutes the primary mineral component of bones, and its crystal structure, along with the surface interaction with proteins, significantly influences the outstanding mechanical properties of bone. This study focuses on natural hydroxyapatite, constructing a surface model with calcium vacancy defects. Employing a representative model of aspartic acid residues, we delve into the adsorption mechanism on the crystal surface and scrutinize the adsorption forms of amino acid residues on HAP and calcium-deficient hydroxyapatite (CDHA) surfaces. The research also explores the impact of different environments on adsorption energy. Furthermore, a simplified sandwich structure of crystal-polypeptide-crystal is presented, analyzing the distribution of amino acid residue adsorption sites on the crystal surface of the polypeptide fragment. This investigation aims to elucidate how the stick–slip mechanism of polypeptide molecules on the crystal surface influences the mechanical properties of the system. By uncovering the interface mechanical behavior between HAP and osteopontin peptides, this article offers valuable theoretical insights for the construction and biomimetic design of biocomposites.

show abstract

Binding Mode Characterization of Osteopontin on Hydroxyapatite by Solution NMR Spectroscopy

Cited by 5 publications

References 67 publications

Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

How phosphorylation impacts intrinsically disordered proteins and their function

The impact of hydroxyapatite crystal structures and protein interactions on bone's mechanical properties

Contact Info

Product

Resources

About