Emulation of the structure of the Saposin protein fold by a lung surfactant peptide construct of surfactant Protein B.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2022
Historique:
received: 04 07 2022
accepted: 14 10 2022
entrez: 3 11 2022
pubmed: 4 11 2022
medline: 8 11 2022
Statut: epublish

Résumé

The three-dimensional structure of the synthetic lung Surfactant Protein B Peptide Super Mini-B was determined using an integrative experimental approach, including mass spectrometry and isotope enhanced Fourier-transform infrared (FTIR) spectroscopy. Mass spectral analysis of the peptide, oxidized by solvent assisted region-specific disulfide formation, confirmed that the correct folding and disulfide pairing could be facilitated using two different oxidative structure-promoting solvent systems. Residue specific analysis by isotope enhanced FTIR indicated that the N-terminal and C-terminal domains have well defined α-helical amino acid sequences. Using these experimentally derived measures of distance constraints and disulfide connectivity, the ensemble was further refined with molecular dynamics to provide a medium resolution, residue-specific structure for the peptide construct in a simulated synthetic lung surfactant lipid multilayer environment. The disulfide connectivity combined with the α-helical elements stabilize the peptide conformationally to form a helical hairpin structure that resembles critical elements of the Saposin protein fold of the predicted full-length Surfactant Protein B structure.

Identifiants

pubmed: 36327300
doi: 10.1371/journal.pone.0276787
pii: PONE-D-22-18838
pmc: PMC9632872
doi:

Substances chimiques

Saposins 0
IgA receptor 0
Pulmonary Surfactants 0
Peptides 0
Surface-Active Agents 0
Disulfides 0
Solvents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0276787

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States

Déclaration de conflit d'intérêts

FW, AW, LG and the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center hold a patent on Super Mini-B (US 8,563,683).

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Auteurs

Alan J Waring (AJ)

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States of America.
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

Julian P Whitelegge (JP)

Jane & Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

Shantanu K Sharma (SK)

Materials and Process Simulation Center, California Institute of Technology, Pasadena, California, United States of America.

Larry M Gordon (LM)

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States of America.

Frans J Walther (FJ)

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States of America.
Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

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