PDBsum entry 6o2v

Signaling protein

PDB id: 6o2v

Contents

Protein chains

135 a.a.

Ligands

FMT

GOL

Waters ×320

PDB id:

6o2v

Name:

Signaling protein

Title:

Crystal structure of the saraf luminal domain cys-lock mutant monomer

Structure:

Store-operated calcium entry-associated regulatory factor. Chain: a, b. Synonym: soce-associated regulatory factor,hbv x-transactivated gene 3 protein,hbv xag-transactivated protein 3,protein foap-7, transmembrane protein 66. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: saraf, tmem66, xtp3, hspc035, npd003, psec0019, unq1967/pro4499. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.58Å R-factor: 0.167 R-free: 0.203

Authors:

C.R.Kimberlin,D.L.Minor

Key ref:

C.R.Kimberlin et al. (2019). SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped β-Sandwich Fold Important for SOCE Modulation. J Mol Biol, 431, 2869-2883. PubMed id: 31082439 DOI: 10.1016/j.jmb.2019.05.008

Date:

24-Feb-19 Release date: 29-May-19

Protein chains

Q96BY9  (SARAF_HUMAN) -  Store-operated calcium entry-associated regulatory factor from Homo sapiens

Seq: 339 a.a.

Struc: 135 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2019.05.008

J Mol Biol 431:2869-2883 (2019)

PubMed id: 31082439

SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped β-Sandwich Fold Important for SOCE Modulation.

C.R.Kimberlin, A.Meshcheriakova, R.Palty, A.Raveh, I.Karbat, E.Reuveny, D.L.Minor.

ABSTRACT

Store-Operated Calcium Entry (SOCE) plays key roles in cell proliferation, muscle contraction, immune responses, and memory formation. The coordinated interactions of a number of proteins from the plasma and endoplasmic reticulum membranes control SOCE to replenish internal Ca²⁺ stores and generate intracellular Ca²⁺ signals. SARAF, an endoplasmic reticulum resident component of the SOCE pathway having no homology to any characterized protein, serves as an important brake on SOCE. Here, we describe the X-ray crystal structure of the SARAF luminal domain, SARAF_L. This domain forms a novel 10-stranded β-sandwich fold that includes a set of three conserved disulfide bonds, denoted the "SARAF-fold." The structure reveals a domain-swapped dimer in which the last two β-strands (β9 and β10) are exchanged forming a region denoted the "SARAF luminal switch" that is essential for dimerization. Sequence comparisons reveal that the SARAF-fold is highly conserved in vertebrates and in a variety of pathologic fungi. Förster resonance energy transfer experiments using full-length SARAF validate the formation of the domain-swapped dimer in cells and demonstrate that dimerization is reversible. A designed variant lacking the SARAF luminal switch shows that the domain swapping is essential to function and indicates that the SARAF dimer accelerates SOCE inactivation.