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Pulmonary surfactant lipid reorganization induced by the adsorption of the oligomeric surfactant protein B Complex

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Liekkinen, Juho and Enkavi, Giray and Javanainen, Matti and Olmeda Lozano, Bárbara and Pérez-Gil, Jesús and Vattulainen, Ilpo (2020) Pulmonary surfactant lipid reorganization induced by the adsorption of the oligomeric surfactant protein B Complex. Journal of Molecular Biology, 432 (10). pp. 3251-3268. ISSN 0022-2836

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Official URL: https://www.sciencedirect.com/science/article/pii/S0022283620302059



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.


Item Type:Article
Uncontrolled Keywords:Pulmonary surfactant; Protein–lipid interactions; SP-B; Molecular dynamics simulation
Subjects:Medical sciences > Biology > Biochemistry
ID Code:62019
Deposited On:08 Sep 2020 10:38
Last Modified:09 Sep 2020 07:58

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