Statistical comparison of ligand-binding kinetics

1989 ◽  
Vol 8 (7) ◽  
pp. 871-881
Author(s):  
John B. Cologne ◽  
Paul M. Mendelman ◽  
Donald O. Chaffin
2008 ◽  
Vol 295 (4) ◽  
pp. H1439-H1450 ◽  
Author(s):  
Parag Pawar ◽  
Sameer Jadhav ◽  
Charles D. Eggleton ◽  
Konstantinos Konstantopoulos

Polymorphonuclear leukocyte (PMN) recruitment to sites of inflammation is initiated by selectin-mediated PMN tethering and rolling on activated endothelium under flow. Cell rolling is modulated by bulk cell deformation (mesoscale), microvillus deformability (microscale), and receptor-ligand binding kinetics (nanoscale). Selectin-ligand bonds exhibit a catch-slip bond behavior, and their dissociation is governed not only by the force but also by the force history. Whereas previous theoretical models have studied the significance of these three “length scales” in isolation, how their interplay affects cell rolling has yet to be resolved. We therefore developed a three-dimensional computational model that integrates the aforementioned length scales to delineate their relative contributions to PMN rolling. Our simulations predict that the catch-slip bond behavior and to a lesser extent bulk cell deformation are responsible for the shear threshold phenomenon. Cells bearing deformable rather than rigid microvilli roll slower only at high P-selectin site densities and elevated levels of shear (≥400 s−1). The more compliant cells (membrance stiffness = 1.2 dyn/cm) rolled slower than cells with a membrane stiffness of 3.0 dyn/cm at shear rates >50 s−1. In summary, our model demonstrates that cell rolling over a ligand-coated surface is a highly coordinated process characterized by a complex interplay between forces acting on three distinct length scales.


1998 ◽  
Vol 75 (3) ◽  
pp. 1553-1572 ◽  
Author(s):  
Scott E. Chesla ◽  
Periasamy Selvaraj ◽  
Cheng Zhu

2019 ◽  
Vol 15 (2) ◽  
pp. 139-153 ◽  
Author(s):  
Monica Bouzo-Lorenzo ◽  
Leigh A. Stoddart ◽  
Lizi Xia ◽  
Adriaan P. IJzerman ◽  
Laura H. Heitman ◽  
...  

2014 ◽  
Vol 465 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Penny Beckerson ◽  
Michael T. Wilson ◽  
Dimitri A. Svistunenko ◽  
Brandon J. Reeder

The redox state of the two-surface exposed cysteine residues in cytoglobin (Cygb) regulates the biochemical and potential physiological properties of the protein. Significant changes to ligand-binding kinetics, peroxidase activity and lipid-binding-induced structural changes are observed.


2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Giuseppe Deganutti ◽  
Andrei Zhukov ◽  
Francesca Deflorian ◽  
Stephanie Federico ◽  
Giampiero Spalluto ◽  
...  

2006 ◽  
Vol 393 (3) ◽  
pp. 749-755 ◽  
Author(s):  
Takuma Shiraki ◽  
Takashi S. Kodama ◽  
Sayaka Shiki ◽  
Tatsuo Nakagawa ◽  
Hisato Jingami

PPARγ (peroxisome proliferator-activated receptor γ) is a nuclear receptor that is activated by natural lipid metabolites, including 15d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2). We previously reported that several oxidized lipid metabolites covalently bind to PPARγ through a Michael-addition to activate transcription. To separate the ligand-entering (dock) and covalent-binding (lock) steps in PPARγ activation, we investigated the binding kinetics of 15d-PGJ2 to the PPARγ LBD (ligand-binding domain) by stopped-flow spectroscopy. We analysed the spectral changes of 15d-PGJ2 by multi-wavelength global fitting based on a two-step chemical reaction model, in which an intermediate state represents the 15d-PGJ2–PPARγ complex without covalent binding. The extracted spectrum of the intermediate state in wild-type PPARγ was quite similar to the observed spectrum of 15d-PGJ2 in the C285S mutant, which cannot be activated by 15d-PGJ2, indicating that the complex remains in the inactive, intermediate state in the mutant. Thus ‘lock’ rather than ‘dock’ is one of the critical steps in PPARγ activation by 15d-PGJ2.


2008 ◽  
Vol 1 (4) ◽  
pp. 276-288 ◽  
Author(s):  
Wei Chen ◽  
Veronika I. Zarnitsyna ◽  
Krishna K. Sarangapani ◽  
Jun Huang ◽  
Cheng Zhu

Sign in / Sign up

Export Citation Format

Share Document