Surfactant protein C explained

Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the SFTPC gene.[1] [2] [3]

It is a membrane protein.

Structure

SFTPC is a 197-residue protein made up of two halves: a unique N-terminal propeptide domain and a C-terminal BRICHOS domain. The around 100-aa long propeptide domain actually contains not only the cleaved part, but also the mature peptide. It can be further broken down into a 23-aa helical transmembrane propeptide proper, the mature secreted SP-C (24-58), and a linker (59-89) that connects to the BRICHOS domain.[4]

The propeptide of pulmonary surfactant C has an N-terminal alpha-helical segment whose suggested function was stabilization of the protein structure, since the mature peptide can irreversibly transform from its native alpha-helical structure to beta-sheet aggregates and form amyloid fibrils. The correct intracellular trafficking of proSP-C has also been reported to depend on the propeptide.[5]

The structure of the BRICHOS domain has been solved. Mutations in this domain also lead to amyloid fibrils made up of the mature peptide, suggesting a chaperone activity.[4]

Clinical significance

Mutations are associated with surfactant metabolism dysfunction type 2.

Humans and animals born lacking SP-C tend to develop progressive interstitial lung disease.

Recombinant SP-C is used in Venticute, an artificial lung surfactant.

A process to mass-produce an analogue called rSP-C33Le by fusion with spidroin has been described.[6]

Further reading

External links

Notes and References

  1. Keller A, Eistetter HR, Voss T, Schäfer KP . The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein . The Biochemical Journal . 277 (Pt 2) . Pt 2 . 493–9 . July 1991 . 1859376 . 1151261 . 10.1042/bj2770493 .
  2. Johansson H, Nordling K, Weaver TE, Johansson J . The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-val transmembrane segment . The Journal of Biological Chemistry . 281 . 30 . 21032–9 . July 2006 . 16709565 . 10.1074/jbc.M603001200 . free .
  3. Web site: Entrez Gene: SFTPC surfactant, pulmonary-associated protein C.
  4. Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keränen H, Hermansson E, Hamvas A, Nogee LM, Bergman T, Saenz A, Casals C, Åqvistg J, Jörnvall H, Berglund H, Presto J, Knight SD, Johansson J . 6 . High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C . Proceedings of the National Academy of Sciences of the United States of America . 109 . 7 . 2325–9 . February 2012 . 22308375 . 3289314 . 10.1073/pnas.1114740109 . 2012PNAS..109.2325W . free .
  5. Li J, Liepinsh E, Almlén A, Thyberg J, Curstedt T, Jörnvall H, Johansson J . Structure and influence on stability and activity of the N-terminal propeptide part of lung surfactant protein C . The FEBS Journal . 273 . 5 . 926–35 . March 2006 . 16478467 . 10.1111/j.1742-4658.2006.05124.x . 1231483 . free .
  6. Kronqvist N, Sarr M, Lindqvist A, Nordling K, Otikovs M, Venturi L, Pioselli B, Purhonen P, Landreh M, Biverstål H, Toleikis Z, Sjöberg L, Robinson CV, Pelizzi N, Jörnvall H, Hebert H, Jaudzems K, Curstedt T, Rising A, Johansson J . 6 . Efficient protein production inspired by how spiders make silk . Nature Communications . 8 . 1 . 15504 . May 2017 . 28534479 . 5457526 . 10.1038/ncomms15504 . 2017NatCo...815504K .