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Pulmonary Surfactant Lipid Reorganization Induced by the Adsorption of the Oligomeric Surfactant Protein B Complex
- Source :
- E-Prints Complutense. Archivo Institucional de la UCM, instname, E-Prints Complutense: Archivo Institucional de la UCM, Universidad Complutense de Madrid
- Publication Year :
- 2020
-
Abstract
- Surfactant protein B (SP-B) is essential in transferring surface-active phospholipids from membrane-based surfactant complexes into the alveolar air-liquid interface. This allows maintaining the mechanical stability of the surfactant film under high pressure at the end of expiration; therefore, SP-B is crucial in lung function. Despite its necessity, the structure and the mechanism of lipid transfer by SP-B have remained poorly characterized. Earlier, we proposed higher-order oligomerization of SP-B into ring-like supramolecular assemblies. In the present work, we used coarse-grained molecular dynamics simulations to elucidate how the ring-like oligomeric structure of SP-B determines its membrane binding and lipid transfer. In particular, we explored how SP-B interacts with specific surfactant lipids, and how consequently SP-B reorganizes its lipid environment to modulate the pulmonary surfactant structure and function. Based on these studies, there are specific lipid-protein interactions leading to perturbation and reorganization of pulmonary surfactant layers. Especially, we found compelling evidence that anionic phospholipids and cholesterol are needed or even crucial in the membrane binding and lipid transfer function of SP-B. Also, on the basis of the simulations, larger oligomers of SP-B catalyze lipid transfer between adjacent surfactant layers. Better understanding of the molecular mechanism of SP-B will help in the design of therapeutic SP-B-based preparations and novel treatments for fatal respiratory complications, such as the acute respiratory distress syndrome. (C) 2020 The Author(s). Published by Elsevier Ltd.
- Subjects :
- Bioquímica
Models, Molecular
MOLECULAR-DYNAMICS SIMULATIONS
Protein Conformation
RESPIRATORY-FAILURE
Lipid Bilayers
Supramolecular chemistry
Protein-lipid interactions
Molecular Dynamics Simulation
MEMBRANES
FILMS
114 Physical sciences
03 medical and health sciences
Molecular dynamics
chemistry.chemical_compound
0302 clinical medicine
Adsorption
Pulmonary surfactant
Structural Biology
Molecular Biology
INTERFACIAL PROPERTIES
Phospholipids
030304 developmental biology
0303 health sciences
Binding Sites
Pulmonary Surfactant-Associated Protein B
SP-B
SP-C
Chemistry
Cholesterol
CHOLESTEROL
Pulmonary Surfactants
Surfactant protein B
Membrane
Mechanical stability
FORCE-FIELD
Biophysics
lipids (amino acids, peptides, and proteins)
STRUCTURE PREDICTION
Protein Multimerization
LUNG
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- E-Prints Complutense. Archivo Institucional de la UCM, instname, E-Prints Complutense: Archivo Institucional de la UCM, Universidad Complutense de Madrid
- Accession number :
- edsair.doi.dedup.....be91fef1a4eb60779686989d35ea48b2