Binding, internalization, and intracellular processing of protein ligands. Derivation of rate constants by computer modeling.

Myers, Alyssa; Kovach, John S.; Vuk‐Pavlović, Stanimir

doi:10.1016/s0021-9258(18)48269-5

Cited by 44 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(D2vlah)1/3 5 X lO-5-10-3 *This is only an analog of the mass transport coefficient; however, like with true kt, its ratio to konR determines the extent to which diffusion affects the rate of binding. et al, 1992; Waters et al, 1990;Myers et al, 1987;Pitas et al, 1979;Wiley, 1988). It is not always realized that the conditions for having a diffusion-limited reaction with a confluent colony differ from those with isolated cells.…”

Section: Discussionmentioning

confidence: 99%

Ligand-receptor interaction rates in the presence of convective mass transport

Model¹,

Omann²

1995

Biophysical Journal

View full text Add to dashboard Cite

The rate of binding of a ligand to receptors on the cell surface can be diffusion limited. We analyze the kinetics of binding, diffusion-limited in a stationary liquid, in the presence of convective mass transport. We derive a formula that expresses the reaction kinetics in terms of the mass transfer coefficient. A moderately transport-limited kinetics is not readily recognizable from the shape of the binding curve and may lead to erroneous estimates of the rate coefficients. We apply our results to practically important cases: a cell suspension in a stirred volume of liquid and a confluent cell colony under a laminar stream. Using typical numbers characterizing the ligand-receptor interactions, we show that stirring and perfusion can be important factors determining the reaction rates. With the confluent colony, the early reaction kinetics requires a different treatment, and we provide it for the case of low receptor occupancy. We show that, even with a fast perfusion, a cell monolayer can transiently generate a zone of depletion of the ligand, and that would affect the early stages of the reaction. Our results are expressed in a simple analytical form and can be used for the design and interpretation of experimental data.

show abstract

Section: Discussionmentioning

confidence: 99%

Ligand-receptor interaction rates in the presence of convective mass transport

Model¹,

Omann²

1995

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…The unbinding rate k u varies between EGFR ligands. EGF has an unbinding rate experimentally measured as 0.02-0.04 s −1 [49], 0.04 s −1 [50], 0.055 s −1 [51], 0.06 s −1 [52], 0.062 s −1 [53], and 0.066 s −1 [54]. Selecting an intermediate value of EGF unbinding from EGF receptors of k u,EGF = 0.05 s −1 , the internalization probability of EGFR following EGF binding is approximately 29% (black circle in figure 2(A)).…”

Section: Proofreadingmentioning

confidence: 99%

Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading

Leblanc,

Sugiyama,

Antonescu

et al. 2023

Phys. Biol.

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology that is stimulated by multiple distinct ligands. Although ligands bind to EGFR while the receptor is exposed on the plasma membrane, EGFR incorporation into endosomes following receptor internalization is an important aspect of EGFR signaling, with EGFR internalization behavior dependent upon the type of ligand bound. We develop quantitative modeling for EGFR recruitment to and internalization from clathrin domains, focusing on how internalization competes with ligand unbinding from EGFR. We develop two model versions: a kinetic model with EGFR behavior described as transitions between discrete states and a spatial model with EGFR diffusion to circular clathrin domains. We find that a combination of spatial and kinetic proofreading leads to enhanced EGFR internalization ratios in comparison to unbinding differences between ligand types. Various stages of the EGFR internalization process, including recruitment to and internalization from clathrin domains, modulate the internalization differences between receptors bound to different ligands. Our results indicate that following ligand binding, EGFR may encounter multiple clathrin domains before successful recruitment and internalization. The quantitative modeling we have developed describes competition between EGFR internalization and ligand unbinding and the resulting proofreading.

show abstract

“…The unbinding rate k u varies between EGFR ligands. EGF has an unbinding rate experimentally measured as 0.02 -0.04 s −1 [49], 0.04 s −1 [50], 0.055 s −1 [51], 0.06 s −1 [52], 0.062 s −1 [53], and 0.066 s −1 [54]. Selecting an intermediate value of EGF unbinding from EGF receptors of k u,EGF = 0.05 s −1 , the internalization probability of EGFR following EGF binding is approximately 29% (black circle in Fig.…”

Section: Proofreadingmentioning

confidence: 99%

Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading

LeBlanc

Sugiyama

Antonescu

et al. 2023

Preprint

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology that is stimulated by multiple distinct ligands. Although ligands bind to EGFR while the receptor is exposed on the plasma membrane, EGFR incorporation into endosomes following receptor internalization is an important aspect of EGFR signaling, with EGFR internalization behavior dependent upon the type of ligand bound. We develop quantitative modeling, both kinetic and with spatial details, for EGFR recruitment to and internalization from clathrin domains and competition with ligand unbinding from EGFR. We find that a combination of spatial and kinetic proofreading leads to enhanced EGFR internalization ratios in comparison to unbinding differences between ligand types. Various stages of the EGFR internalization process, including recruitment to and internalization from clathrin domains, modulate the internalization differences between receptors bound to different ligands. Our results indicate that following ligand binding, EGFR may encounter multiple clathrin domains before successful recruitment and internalization. The quantitative modeling we have developed describes competition between EGFR internalization and ligand unbinding and the resulting proofreading.

show abstract

Binding, internalization, and intracellular processing of protein ligands. Derivation of rate constants by computer modeling.

Cited by 44 publications

References 16 publications

Ligand-receptor interaction rates in the presence of convective mass transport

Ligand-receptor interaction rates in the presence of convective mass transport

Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading

Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading

Contact Info

Product

Resources

About