PDBsum entry 4yhc

Structural protein

PDB id: 4yhc

Contents

Protein chains

439 a.a.

411 a.a.

Ligands

CIT ×2

Waters ×307

PDB id:

4yhc

Name:

Structural protein

Title:

Crystal structure of the wd40 domain of scap from fission yeast

Structure:

Sterol regulatory element-binding protein cleavage- activating protein. Chain: a, b. Fragment: unp residues 567-961, linker (ags) and residues 986-1054. Synonym: srebp cleavage-activating protein,srebp cleavage-activating protein. Engineered: yes. Mutation: yes

Source:

Schizosaccharomyces pombe (strain 972 / atcc 24843). Fission yeast. Organism_taxid: 284812. Strain: 972 / atcc 24843. Gene: scp1, spbc3b9.15c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.05Å R-factor: 0.180 R-free: 0.229

Authors:

X.Gong,J.X.Li,J.P.Wu,C.Y.Yan,N.Yan

Key ref:

X.Gong et al. (2015). Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition. Cell Res, 25, 401-411. PubMed id: 25771684 DOI: 10.1038/cr.2015.32

Date:

27-Feb-15 Release date: 01-Apr-15

Protein chain

O43043  (SCAP_SCHPO) -  Sterol regulatory element-binding protein cleavage-activating protein from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 1086 a.a.

Struc: 439 a.a.*

Protein chain

O43043  (SCAP_SCHPO) -  Sterol regulatory element-binding protein cleavage-activating protein from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 1086 a.a.

Struc: 411 a.a.*

* PDB and UniProt seqs differ at 18 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1038/cr.2015.32

Cell Res 25:401-411 (2015)

PubMed id: 25771684

Structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition.

X.Gong, J.Li, W.Shao, J.Wu, H.Qian, R.Ren, P.Espenshade, N.Yan.

ABSTRACT

The 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 Å resolution. The structure reveals an eight-bladed β-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.