Membrane curvature recognition by C-reactive protein using lipoprotein mimics

Wang, Min S.; Messersmith, Reid E.; Reed, Scott M.

doi:10.1039/c2sm25779c

Cited by 27 publications

(30 citation statements)

References 65 publications

(174 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A significant portion of 3H12 signal was found to be cell-associated. This is consistent with the previously described membrane pathway of CRP to mCRP conversion [3,10,14,16,17,22,26,27]. Previous studies have demonstrated the extrahepatic CRP expression by kidney [6] and in atherosclerotic plaques [28], however, it remains uncertain whether the expression product is pentameric CRP or mCRP.…”

Section: Discussionsupporting

confidence: 80%

Immunohistochemical staining reveals C-reactive protein existing predominantly as altered conformation forms in inflammatory lesions

Shi¹,

Li²,

Zhu³

et al. 2014

Acta Biologica Hungarica

View full text Add to dashboard Cite

C-reactive protein (CRP) is an established marker of inflammation and has been proposed to play a proinflammatory role in pathologies of several diseases. CRP is primarily produced by the liver and released into circulation as a pentameric molecule composed of five identical subunits. It has been suggested that the activation of the proinflammatory actions of CRP requires sequential conformational changes triggered by local inflammatory conditions. These include the dissociation into the subunit form (monomeric CRP, mCRP) and further reduction of the intra-subunit disulfide bond of mCRP. This model predicts that mCRP is the primary isoform present in inflamed but not healthy tissues, however the supporting evidence is lacking. Herein, we stained tissue samples across multiple anatomical locations from several types of human diseases with highly selective monoclonal antibodies that can differentiate CRP and mCRP. The results indicated that mCRP is the predominant form existing in the lesions. Further immunoblotting of the patient tissue samples revealed the potential presence of reduced mCRP. Together, we conclude that mCRP but not CRP is the major isoform present in local inflammatory lesions, supporting the so-called cascading model of CRP function and regulation.

show abstract

Section: Discussionsupporting

confidence: 80%

Immunohistochemical staining reveals C-reactive protein existing predominantly as altered conformation forms in inflammatory lesions

Shi¹,

Li²,

Zhu³

et al. 2014

Acta Biologica Hungarica

View full text Add to dashboard Cite

show abstract

“…47 We have previously shown that GNP-PC-DT (≤28 nm) binds to CRP when calcium is present. 26 When this binding is observed by tracking the LSPR, the addition of CRP causes changes in the centroid, OD, and FWHM (Figure 6) that results from two distinct events.…”

Section: Resultsmentioning

confidence: 99%

“…13 Unlike nanohole supported membranes, 23 GNPs provide precise control of curvature without planar membrane regions or regions of negative curvature. Hybrid membranes consisting of one outer leaflet of lipid and an inner leaflet of alkanethiol have been prepared on spherical GNPs with 6, 25 10, 26 12, 27 16, 27 and 18 28 carbon alkanethiol chain lengths and on gold nanoshells with 12 29 and 18 30 carbon alkanethiol chain lengths providing many systems in which LSPR tracking could be used to understand membrane assembly and to observe protein binding. While many systems have been synthesized, LSPR tracking has not been used to monitor membrane assembly or protein binding.…”

Section: Introductionmentioning

confidence: 99%

Using the Localized Surface Plasmon Resonance of Gold Nanoparticles To Monitor Lipid Membrane Assembly and Protein Binding

2013

Self Cite

View full text Add to dashboard Cite

Gold nanoparticles provide a template for preparing supported lipid layers with well-defined curvature. Here, we utilize the localized surface plasmon resonance (LSPR) of gold nanoparticles as a sensor for monitoring the preparation of lipid layers on nanoparticles. The LSPR is very sensitive to the immediate surroundings of the nanoparticle surface and it is used to monitor the coating of lipids and subsequent conversion of a supported bilayer to a hybrid membrane with an outer lipid leaflet and an inner leaflet containing hydrophobic alkanethiol. We demonstrate that both decanethiol and propanethiol are able to form hybrid membranes and that the membrane created over the shorter thiol can be stripped from the gold along with the lipid leaflet using β-mercaptoethanol. The sensitivity of the nanoparticle LSPR to the refractive index (RI) of its surroundings is greater when the shorter thiol is used (37.8 ± 1.5 nm per RI unit) than when the longer thiol is used (27.5 ± 0.5 nm per RI unit). Finally, C-reactive protein binding to the membrane is measured using this sensor allowing observation of both protein-membrane and nanoparticle-nanoparticle interactions without chemical labeling of protein or lipids.

show abstract

“…3a–d), increases the fluid nature (CHO and LPC) and the curvature (LPC) of the lipid bilayer further exposing the phosphocholine and phosphoethanolamine head groups of PC, LPC, SM, PE and LPE lipids373839. Adjacent pCRP subunits (that is, CRP monomers) are held together by nine salt bridges, three hydrogen bonds and ten nonpolar interactions.…”

Section: Resultsmentioning

confidence: 99%

Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

et al. 2017

View full text Add to dashboard Cite

C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions.

show abstract

Membrane curvature recognition by C-reactive protein using lipoprotein mimics

Cited by 27 publications

References 65 publications

Immunohistochemical staining reveals C-reactive protein existing predominantly as altered conformation forms in inflammatory lesions

Immunohistochemical staining reveals C-reactive protein existing predominantly as altered conformation forms in inflammatory lesions

Using the Localized Surface Plasmon Resonance of Gold Nanoparticles To Monitor Lipid Membrane Assembly and Protein Binding

Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

Contact Info

Product

Resources

About