SDF2L1, a component of the endoplasmic reticulum chaperone complex, differentially interacts with {alpha}-, {beta}-, and {theta}-defensin propeptides.
Mammalian defensins are cationic antimicrobial peptides that play a central role in host innate immunity and as regulators of acquired immunity. In animals, three structural defensin subfamilies, designated as alpha, beta, and , have been characterized, each possessing a distinctive tridisulfide motif. Mature alpha- and beta-defensins are produced by simple proteolytic processing of their prepropeptide precursors. In contrast, the macrocyclic -defensins are formed by the head-to-tail splicing of nonapeptides excised from a pair of prepropeptide precursors. Thus, elucidation of the -defensin biosynthetic pathway provides an opportunity to identify novel factors involved in this unique process. We incorporated the -defensin precursor, proRTD1a, into a bait construct for a yeast two-hybrid screen that identified rhesus macaque stromal cell-derived factor 2-like protein 1 (SDF2L1), as an interactor. SDF2L1 is a component of the endoplasmic reticulum (ER) chaperone complex, which we found to also interact with alpha- and beta-defensins. However, analysis of the SDF2L1 domain requirements for binding of representative alpha-, beta-, and -defensins revealed that alpha- and beta-defensins bind SDF2L1 similarly, but differently from the interactions that mediate binding of SDF2L1 to pro--defensins. Thus, SDF2L1 is a factor involved in processing and/or sorting of all three defensin subfamilies.
Tongaonkar
Prasad
P
Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, Irvine, California 92697, USA. ptongaon@uci.edu
Selsted
Michael E
ME
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow; D023082:Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D047468:Immunoprecipitation; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D022423:Myeloid Cells; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D023084:alpha-Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D023083:beta-Defensins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D023082:Defensins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011498:Protein Precursors; D023084:alpha-Defensins; D023083:beta-Defensins; C450142:theta-defensin; D005982:Glutathione Transferase