Deciphering the Energy Landscape of the Interaction Uranyl-DCP with Antibodies Using Dynamic Force Spectroscopy

Teulon, Jean‐Marie; Parot, Pierre; Odorico, Michaël; Pellequer, Jean‐Luc

doi:10.1529/biophysj.108.141937

Cited by 6 publications

(5 citation statements)

References 14 publications

(20 reference statements)

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“…Very few experiments have stressed on the study of multiple-bond ruptures (Hukkanen et al, 2005;Levy and Maaloum, 2005;Sulchek et al, 2005;Odorico et al, 2007b;Teulon et al, 2007;Tsukasaki et al, 2007;Erdmann et al, 2008;Guo et al, 2008;Teulon et al, 2008), a likely reason may be due to the difficulty in perceiving the distribution form of data that were collected and analyzed from the force-displacement (FD) curves obtained at different loading rates. The effective loading rate (r e ), is related to the critical force that ruptures the interaction between the functionalized tip and the molecules on the substrate surface (Odorico et al, 2007b).…”

Section: Multiple Parallel Bonding and Massive Data Analysismentioning

confidence: 99%

Single and multiple bonds in (strept)avidin–biotin interactions

Teulon

Delcuze

Odorico

et al. 2011

J of Molecular Recognition

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Thanks to Dynamic Force Spectroscopy (DFS) and developments of massive data analysis tools, such as YieldFinder, Atomic Force Microscopy (AFM) becomes a powerful method for analyzing long lifetime ligand-receptor interactions. We have chosen the well-known system, (strept)avidin-biotin complex, as an experimental model due to the lack of consensus on interpretations of the rupture force spectrum (Walton et al., 2008). We present new measurements of force-displacement curves for the (strept)avidin-biotin complex. These data were analyzed using the YieldFinder software based on the Bell-Evans formalism. In addition, the Williams model was adopted to interpret the bonding state of the system. Our results indicate the presence of at least two energy barriers in two loading rate regimes. Combining with structural analysis, the energy barriers can be interpreted in a novel physico-chemical context as one inner barrier for H-bond ruptures ( <1 Å), and one outer barrier for escaping from the binding pocket which is blocked by the side chain of a symmetry-related Trp120 in the streptavidin tetramer. In each loading rate regime, the presence of multiple parallel bonds was implied by the Williams model. Interestingly, we found that in literature different terms created for addressing the apparent discrepancies in the results of avidin-biotin interactions can be reconciled by taking into account multiple parallel bonds.

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Section: Multiple Parallel Bonding and Massive Data Analysismentioning

confidence: 99%

Single and multiple bonds in (strept)avidin–biotin interactions

Teulon

Delcuze

Odorico

et al. 2011

J of Molecular Recognition

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“…The kinetics of the gp120–2G12 interaction and the influence of individual oligomannoside arms of Man 9 (GlcNAc) 2 such as the Man 4 arm and the Man 5 arm have been measured by NMR , and SPR methods ,, but never by single-molecule experiments. The atomic force microscope (AFM) has been widely used to measure the kinetic parameters of a variety of receptor–ligand interactions at the single-molecule level, including carbohydrate–carbohydrate, − carbohydrate–protein, − and antibody–antigen interactions. − In immunology, single-molecule force spectroscopy (SMFS) has been used to study the gp120–CD4 bond on live cells and the interaction of whole viruses with their receptors. , …”

Section: Introductionmentioning

confidence: 99%

Dissecting the Carbohydrate Specificity of the Anti-HIV-1 2G12 Antibody by Single-Molecule Force Spectroscopy

et al. 2012

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Broadly neutralizing anti-HIV-1 monoclonal antibody 2G12 exclusively targets a conserved cluster of high-mannose oligosaccharides present on outer viral envelope glycoprotein gp120. This characteristic makes the otherwise immunogenically "silent" glycan shield of gp120 a tempting target for drug and vaccine design. However, immune responses against carbohydrate-based mimics of gp120 have failed to provide immunization against HIV-1 infection, highlighting the need to understand the molecular events that determine immunogenicity better. In this work, the unbinding kinetics of the gp120-2G12 (k(0) = 0.002 ± 0.09 s(-1), x(++) = 1.5 ± 1.2 nm), Man(4)-2G12 (k(0) = 0.35 ± 0.32 s(-1), x(++) = 0.6 ± 0.2 nm), and Man(5)-2G12 interactions were measured by single-molecule force spectroscopy. To our knowledge, this is the first single-molecule study aimed at dissecting the carbohydrate-antibody recognition of the gp120-2G12 interaction. We were able to confirm crystallographic models that show both the binding of the linear Man(4) arm to 2G12 and also the multivalent gp120 glycan binding to 2G12. These results demonstrate that single-molecule force spectroscopy can be successfully used to dissect the molecular mechanisms underlying immunity.

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“…Considering the large industrial use of uranium, UO 2 2+ has been the subject of many toxicological studies that revealed its ability to interact with a large variety of biochemical targets. Recent investigations included analysis of specific metal carriers,5–8 of human serum proteins,9, 10 and both proteomic and transcriptomic studies to identify proteins related to cellular impacts 11, 12…”

Section: Introductionmentioning

confidence: 99%

Predicting the disruption by UO₂²⁺ of a protein‐ligand interaction

et al. 2010

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The uranyl cation (UO 2 21 ) can be suspected to interfere with the binding of essential metal cations to proteins, underlying some mechanisms of toxicity. A dedicated computational screen was used to identify UO 2 21 binding sites within a set of nonredundant protein structures. The list of potential targets was compared to data from a small molecules interaction database to pinpoint specific examples where UO 2 21 should be able to bind in the vicinity of an essential cation, and would be likely to affect the function of the corresponding protein. The C-reactive protein appeared as an interesting hit since its structure involves critical calcium ions in the binding of phosphorylcholine. Biochemical experiments confirmed the predicted binding site for UO 2 21 and it was demonstrated by surface plasmon resonance assays that UO 2 21 binding to CRP prevents the calcium-mediated binding of phosphorylcholine. Strikingly, the apparent affinity of UO 2 21 for native CRP was almost 100-fold higher than that of Ca 21 . This result exemplifies in the case of CRP the capability of our computational tool to predict effective binding sites for UO 2 21 in proteins and is a first evidence of calcium substitution by the uranyl cation in a native protein.

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Deciphering the Energy Landscape of the Interaction Uranyl-DCP with Antibodies Using Dynamic Force Spectroscopy

Cited by 6 publications

References 14 publications

Single and multiple bonds in (strept)avidin–biotin interactions

Single and multiple bonds in (strept)avidin–biotin interactions

Dissecting the Carbohydrate Specificity of the Anti-HIV-1 2G12 Antibody by Single-Molecule Force Spectroscopy

Predicting the disruption by UO₂²⁺ of a protein‐ligand interaction

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Deciphering the Energy Landscape of the Interaction Uranyl-DCP with Antibodies Using Dynamic Force Spectroscopy

Cited by 6 publications

References 14 publications

Single and multiple bonds in (strept)avidin–biotin interactions

Single and multiple bonds in (strept)avidin–biotin interactions

Dissecting the Carbohydrate Specificity of the Anti-HIV-1 2G12 Antibody by Single-Molecule Force Spectroscopy

Predicting the disruption by UO22+ of a protein‐ligand interaction

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Predicting the disruption by UO₂²⁺ of a protein‐ligand interaction