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

• Pérez-Gil J . Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics . Pediatric Pathology & Molecular Medicine . 20 . 6 . 445–69 . 2002 . 11699574 . 10.1080/15227950152625783 .
• Solarin KO, Wang WJ, Beers MF . Synthesis and post-translational processing of surfactant protein C . Pediatric Pathology & Molecular Medicine . 20 . 6 . 471–500 . 2002 . 11699575 . 10.1080/15227950152625792 .
• Johansson J, Curstedt T, Robertson B . Artificial surfactants based on analogues of SP-B and SP-C . Pediatric Pathology & Molecular Medicine . 20 . 6 . 501–18 . 2002 . 11699576 . 10.1080/15227950152625800 .
• Nogee LM . Alterations in SP-B and SP-C expression in neonatal lung disease . Annual Review of Physiology . 66 . 601–23 . 2004 . 14977415 . 10.1146/annurev.physiol.66.032102.134711 .
• Brasch F, Griese M, Tredano M, Johnen G, Ochs M, Rieger C, Mulugeta S, Müller KM, Bahuau M, Beers MF . 6 . Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene . The European Respiratory Journal . 24 . 1 . 30–9 . July 2004 . 15293602 . 10.1183/09031936.04.00000104 . free .
• Curstedt T, Johansson J, Persson P, Eklund A, Robertson B, Löwenadler B, Jörnvall H . Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups . Proceedings of the National Academy of Sciences of the United States of America . 87 . 8 . 2985–9 . April 1990 . 2326260 . 53818 . 10.1073/pnas.87.8.2985 . 1990PNAS...87.2985C . free .
• Simatos GA, Forward KB, Morrow MR, Keough KM . Interaction between perdeuterated dimyristoylphosphatidylcholine and low molecular weight pulmonary surfactant protein SP-C . Biochemistry . 29 . 24 . 5807–14 . June 1990 . 2383558 . 10.1021/bi00476a023 .
• Glasser SW, Korfhagen TR, Perme CM, Pilot-Matias TJ, Kister SE, Whitsett JA . Two SP-C genes encoding human pulmonary surfactant proteolipid . The Journal of Biological Chemistry . 263 . 21 . 10326–31 . July 1988 . 10.1016/S0021-9258(19)81519-3 . 2839484 . free .
• Glasser SW, Korfhagen TR, Weaver TE, Clark JC, Pilot-Matias T, Meuth J, Fox JL, Whitsett JA . 6 . cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal) . The Journal of Biological Chemistry . 263 . 1 . 9–12 . January 1988 . 10.1016/S0021-9258(19)57347-1 . 3335510 . free .
• Johansson J, Jörnvall H, Eklund A, Christensen N, Robertson B, Curstedt T . Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms . FEBS Letters . 232 . 1 . 61–4 . May 1988 . 3366248 . 10.1016/0014-5793(88)80386-7 . 29388224 . free .
• Warr RG, Hawgood S, Buckley DI, Crisp TM, Schilling J, Benson BJ, Ballard PL, Clements JA, White RT . 6 . Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences . Proceedings of the National Academy of Sciences of the United States of America . 84 . 22 . 7915–9 . November 1987 . 3479771 . 299446 . 10.1073/pnas.84.22.7915 . 1987PNAS...84.7915W . free .
• Young WA . Familial fibrocystic pulmonary dysplasia: a new case in a known affected family . Canadian Medical Association Journal . 94 . 20 . 1059–61 . May 1966 . 5942662 . 1935417 .
• Wood S, Yaremko ML, Schertzer M, Kelemen PR, Minna J, Westbrook CA . Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and characterization of a microsatellite repeat marker that shows frequent loss of heterozygosity in human carcinomas . Genomics . 24 . 3 . 597–600 . December 1994 . 7713515 . 10.1006/geno.1994.1673 .
• Hatzis D, Deiter G, deMello DE, Floros J . Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species . Experimental Lung Research . 20 . 1 . 57–72 . 1994 . 8181452 . 10.3109/01902149409064373 .
• Nogee LM, Dunbar AE, Wert SE, Askin F, Hamvas A, Whitsett JA . A mutation in the surfactant protein C gene associated with familial interstitial lung disease . The New England Journal of Medicine . 344 . 8 . 573–9 . February 2001 . 11207353 . 10.1056/NEJM200102223440805 . free .
• Glasser SW, Burhans MS, Korfhagen TR, Na CL, Sly PD, Ross GF, Ikegami M, Whitsett JA . 6 . Altered stability of pulmonary surfactant in SP-C-deficient mice . Proceedings of the National Academy of Sciences of the United States of America . 98 . 11 . 6366–71 . May 2001 . 11344267 . 33474 . 10.1073/pnas.101500298 . 2001PNAS...98.6366G . free .

External links

• GeneReviews/NIH/NCBI/UW entry on Pulmonary Fibrosis, Familial

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 .