RT Journal Article
T1 Dimerization of the pulmonary surfactant protein C in a membrane environment
A1 Korolainen, Hanna
A1 Lolicato, Fabio
A1 Enkavi, Giray
A1 Pérez Gil, Jesús
A1 Kulig, Waldemar
A1 Vattulainen, Ilpo
AB Surfactant protein C (SP-C) has several functions in pulmonary surfactant. These include the transfer of lipids between different membrane structures, a role in surfactant recycling and homeostasis, and involvement in modulation of the innate defense system. Despite these important functions, the structures of functional SP-C complexes have remained unclear. SP-C is known to exist as a primarily α-helical structure with an apparently unstructured N-terminal region, yet there is recent evidence that the functions of SP-C could be associated with the formation of SP-C dimers and higher oligomers. In this work, we used molecular dynamics simulations, two-dimensional umbrella sampling, and well-tempered metadynamics to study the details of SP-C dimerization. The results suggest that SP-C dimerizes in pulmonary surfactant membranes, forming dimers of different topologies. The simulations identified a dimerization motif region V21xxxVxxxGxxxM33 that is much larger than the putative A30xxxG34 motif that is commonly assumed to control the dimerization of some α-helical transmembrane domains. The results provide a stronger basis for elucidating how SP-C functions in concert with other surfactant proteins.
PB Public Library Science
SN 1932-6203
YR 2022
FD 2022-04-27
LK https://hdl.handle.net/20.500.14352/71853
UL https://hdl.handle.net/20.500.14352/71853
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Academy of Finland
NO Doctoral Programme in Materials Research and Nanosciences (MATRENA)
DS Docta Complutense
RD 4 may 2024