6O2U

Crystal structure of the SARAF luminal domain

6O2U の概要

• エントリーDOI: 10.2210/pdb6o2u/pdb
• 分子名称: Store-operated calcium entry-associated regulatory factor (2 entities in total)
• 機能のキーワード: soce, store operated calcium entry, saraf, er, endoplasmic reticulum, calcium signaling, domain swap, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31034.61

構造登録者

Kimberlin, C.R.,Minor, D.L. (登録日: 2019-02-24, 公開日: 2019-05-29, 最終更新日: 2024-11-06)

主引用文献

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

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: 31082439
DOI: 10.1016/j.jmb.2019.05.008

実験手法

X-RAY DIFFRACTION (1.8 Å)