6O2W
Crystal structure of the SARAF luminal domain Cys-lock mutant dimer
Summary for 6O2W
| Entry DOI | 10.2210/pdb6o2w/pdb |
| Related | 6O2U 6O2V |
| Descriptor | Store-operated calcium entry-associated regulatory factor, GLYCEROL (3 entities in total) |
| Functional Keywords | soce, store operated calcium entry, saraf, er, endoplasmic reticulum, calcium signaling, domain swap, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 31138.76 |
| Authors | Kimberlin, C.R.,Minor, D.L. (deposition date: 2019-02-24, release date: 2019-05-29, Last modification date: 2024-10-23) |
| Primary citation | Kimberlin, C.R.,Meshcheriakova, A.,Palty, R.,Raveh, A.,Karbat, I.,Reuveny, E.,Minor Jr., D.L. SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped beta-Sandwich Fold Important for SOCE Modulation. J.Mol.Biol., 431:2869-2883, 2019 Cited by PubMed 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 Ca stores and generate intracellular Ca 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. 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. PubMed: 31082439DOI: 10.1016/j.jmb.2019.05.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.101 Å) |
Structure validation
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