4yhc
Crystal structure of the WD40 domain of SCAP from fission yeastCrystal structure of the WD40 domain of SCAP from fission yeast
Structural highlights
FunctionSCAP_SCHPO Escort protein required for sre1 processing at low sterol as well as oxygen levels. May regulate export of the scp1/sre1 complex from the ER at low sterol or oxygen levels. 4-methyl sterols bound to scp1 may mask an ER-export signal in scp1 leading to retention of the complex in the ER. Release of 4-methyl sterols may trigger a conformational change in the SSC domain of scp1 unmasking the ER export signal leading to recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of sre1 in the Golgi, release of the transcription factor fragment of sre1 from the membrane, its import into the nucleus and up-regulation of genes required for ergosterol biosynthesis as well as anaerobic growth.[UniProtKB:P97260][1] [2] Publication Abstract from PubMedThe sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating protein (SCAP) are central players in the SREBP pathway, which control the cellular lipid homeostasis. SCAP binds to SREBP through their carboxyl (C) domains and escorts SREBP from the endoplasmic reticulum to the Golgi upon sterol depletion. A conserved pathway, with the homologues of SREBP and SCAP being Sre1 and Scp1, was identified in fission yeast Schizosaccharomyces pombe. Here we report the in vitro reconstitution of the complex between the C domains of Sre1 and Scp1 as well as the crystal structure of the WD40 domain of Scp1 at 2.1 A resolution. The structure reveals an eight-bladed beta-propeller that exhibits several distinctive features from a canonical WD40 repeat domain. Structural and biochemical characterization led to the identification of two Scp1 elements that are involved in Sre1 recognition, an Arg/Lys-enriched surface patch on the top face of the WD40 propeller and a 30-residue C-terminal tail. The structural and biochemical findings were corroborated by in vivo examinations. These studies serve as a framework for the mechanistic understanding and further functional characterization of the SREBP and SCAP proteins in fission yeast and higher organisms.Cell Research advance online publication 13 March 2015; doi:10.1038/cr.2015.32. Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition.,Gong X, Li J, Shao W, Wu J, Qian H, Ren R, Espenshade P, Yan N Cell Res. 2015 Mar 13. doi: 10.1038/cr.2015.32. PMID:25771684[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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