An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B.
The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary surfactant-associated polypeptide SP-B exhibit 24% residue identities (49% similarities), including six half-cystine residues in the same disulphide bonding pattern, and similar far-UV circular dichroism spectra corresponding to 45-55% alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the conformations of NK-lysin and SP-B are similar. In contrast, the functional properties of the two proteins are dissimilar: SP-B does not exhibit antibacterial activity and NK-lysin does not significantly effect phospholipid spreading at an air/water interface. Saposins, which solubilize lipids and activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities with NK-lysin (and SP-B), including the six conserved half-cystine residues. The inclusion of NK-lysin extends the family of saposin-like polypeptides, all members of which appear to interact with lipids. Strictly conserved structural features with implications for helix topology and lipid interactions are observed.
Andersson
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Curstedt
T
T
Jörnvall
H
H
Johansson
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D007421:Intestine, Small / Q000737:chemistry; D008823:Micelles; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013499:Surface Properties; D013552:Swine
D008823:Micelles; C093238:NK-lysin; D011510:Proteolipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine