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Hetero-Multivalency of Pseudomonas aeruginosa Lectin LecA Binding to Model Membranes
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- A single glycan-lectin interaction is often weak and semi-specific. Multiple binding domains in a single lectin can bind with multiple glycan molecules simultaneously, making it difficult for the classic “lock-and-key” model to explain these interactions. We demonstrated that hetero-multivalency, a homo-oligomeric protein simultaneously binding to at least two types of ligands, influences LecA (a Pseudomonas aeruginosa adhesin)-glycolipid recognition. We also observed enhanced binding between P. aeruginosa and mixed glycolipid liposomes. Interestingly, strong ligands could activate weaker binding ligands leading to higher LecA binding capacity. This hetero-multivalency is probably mediated via a simple mechanism, Reduction of Dimensionality (RD). To understand the influence of RD, we also modeled LecA’s two-step binding process with membranes using a kinetic Monte Carlo simulation. The simulation identified the frequency of low-affinity ligand encounters with bound LecA and the bound LecA’s retention of the low-affinity ligand as essential parameters for triggering hetero-multivalent binding, agreeing with experimental observations. The hetero-multivalency can alter lectin binding properties, including avidities, capacities, and kinetics, and therefore, it likely occurs in various multivalent binding systems. Using hetero-multivalency concept, we also offered a new strategy to design high-affinity drug carriers for targeted drug delivery.
- Subjects :
- 0301 basic medicine
Glycan
lcsh:Medicine
Ligands
Article
03 medical and health sciences
Glycolipid
lcsh:Science
Adhesins, Bacterial
Liposome
Multidisciplinary
biology
Chemistry
Ligand
lcsh:R
Lectin
Kinetics
030104 developmental biology
Membrane
Targeted drug delivery
Liposomes
Pseudomonas aeruginosa
biology.protein
Biophysics
lcsh:Q
Drug carrier
Monte Carlo Method
Protein Binding
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....8f85fc7c6778000a48e24ba1a607e187