Limits...
Molecular mechanisms of STIM/Orai communication.

Derler I, Jardin I, Romanin C - Am. J. Physiol., Cell Physiol. (2016)

Bottom Line: Functional as well as mutagenesis studies together with structural insights about STIM and Orai proteins provide a molecular picture of the interplay of these two key players in the CRAC signaling cascade.This review focuses on the main experimental advances in the understanding of the STIM1-Orai choreography, thereby establishing a portrait of key mechanistic steps in the CRAC channel signaling cascade.The focus is on the activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and the consequent structural rearrangements that gate the Orai channels into the open state to allow Ca(2+)permeation into the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Johannes Kepler University of Linz, Linz, Austria; and.

No MeSH data available.


Stromal interaction molecule 1 (STIM1). A: scheme depicts full-length, human STIM1 with regions essential for the STIM1/Orai1 signaling cascade. Insets: structures of the EF-sterile-α-motif (SAM) domain, the STIM1 coiled-coil domain (CC)1α3-CC2 fragment as well as the STIM1 SOAR (344–442) fragment. ER, endoplasmic reticulum; OASF, Orai1 activating STIM1 fragment; CTID, COOH-terminal inhibitory domain; TRIP, Thr-Arg-Ile-Pro sequence. B: crystallographic structure of a STIM1 SOAR (344–442) dimer, exhibiting a V-shaped form, includes CC2 and CC3. Amino acids involved in dimer interaction as well as those mediating coupling to Orai1 (positively charged residues) are highlighted. Left inset: magnified view of interacting residues between the NH2-terminal portion of SOAR monomer “a” and the COOH-terminal portion of SOAR monomer “b.” Right inset: NMR structure of a STIM1 CC1α3-CC2 dimer. The STIM1 CC1α3-CC2 monomers kink between the 2 coiled-coil domains and form dimers via coupling in an antiparallel manner. C: hypothetical model of STIM1 in the resting state.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835918&req=5

Figure 1: Stromal interaction molecule 1 (STIM1). A: scheme depicts full-length, human STIM1 with regions essential for the STIM1/Orai1 signaling cascade. Insets: structures of the EF-sterile-α-motif (SAM) domain, the STIM1 coiled-coil domain (CC)1α3-CC2 fragment as well as the STIM1 SOAR (344–442) fragment. ER, endoplasmic reticulum; OASF, Orai1 activating STIM1 fragment; CTID, COOH-terminal inhibitory domain; TRIP, Thr-Arg-Ile-Pro sequence. B: crystallographic structure of a STIM1 SOAR (344–442) dimer, exhibiting a V-shaped form, includes CC2 and CC3. Amino acids involved in dimer interaction as well as those mediating coupling to Orai1 (positively charged residues) are highlighted. Left inset: magnified view of interacting residues between the NH2-terminal portion of SOAR monomer “a” and the COOH-terminal portion of SOAR monomer “b.” Right inset: NMR structure of a STIM1 CC1α3-CC2 dimer. The STIM1 CC1α3-CC2 monomers kink between the 2 coiled-coil domains and form dimers via coupling in an antiparallel manner. C: hypothetical model of STIM1 in the resting state.

Mentions: STIM proteins (Fig. 1) are single TM proteins with an NH2-terminal portion including the Ca2+-sensing domain localized within the ER lumen and a long cytosolic strand, which couples to Orai channels in the PM. The STIM NH2 and COOH termini are separated by an ∼20-amino acid (aa) TM region (18, 84, 137) (Fig. 1A). The NH2-terminal portion is well conserved from worms and flies to humans, while the COOH-terminal portions are rather divergent among different species (20). The variety of STIM proteins is further extended by diverse splice variants like STIM1L (30) and a STIM2 splice variant (STIM2β, STIM2.1) (104, 136).


Molecular mechanisms of STIM/Orai communication.

Derler I, Jardin I, Romanin C - Am. J. Physiol., Cell Physiol. (2016)

Stromal interaction molecule 1 (STIM1). A: scheme depicts full-length, human STIM1 with regions essential for the STIM1/Orai1 signaling cascade. Insets: structures of the EF-sterile-α-motif (SAM) domain, the STIM1 coiled-coil domain (CC)1α3-CC2 fragment as well as the STIM1 SOAR (344–442) fragment. ER, endoplasmic reticulum; OASF, Orai1 activating STIM1 fragment; CTID, COOH-terminal inhibitory domain; TRIP, Thr-Arg-Ile-Pro sequence. B: crystallographic structure of a STIM1 SOAR (344–442) dimer, exhibiting a V-shaped form, includes CC2 and CC3. Amino acids involved in dimer interaction as well as those mediating coupling to Orai1 (positively charged residues) are highlighted. Left inset: magnified view of interacting residues between the NH2-terminal portion of SOAR monomer “a” and the COOH-terminal portion of SOAR monomer “b.” Right inset: NMR structure of a STIM1 CC1α3-CC2 dimer. The STIM1 CC1α3-CC2 monomers kink between the 2 coiled-coil domains and form dimers via coupling in an antiparallel manner. C: hypothetical model of STIM1 in the resting state.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835918&req=5

Figure 1: Stromal interaction molecule 1 (STIM1). A: scheme depicts full-length, human STIM1 with regions essential for the STIM1/Orai1 signaling cascade. Insets: structures of the EF-sterile-α-motif (SAM) domain, the STIM1 coiled-coil domain (CC)1α3-CC2 fragment as well as the STIM1 SOAR (344–442) fragment. ER, endoplasmic reticulum; OASF, Orai1 activating STIM1 fragment; CTID, COOH-terminal inhibitory domain; TRIP, Thr-Arg-Ile-Pro sequence. B: crystallographic structure of a STIM1 SOAR (344–442) dimer, exhibiting a V-shaped form, includes CC2 and CC3. Amino acids involved in dimer interaction as well as those mediating coupling to Orai1 (positively charged residues) are highlighted. Left inset: magnified view of interacting residues between the NH2-terminal portion of SOAR monomer “a” and the COOH-terminal portion of SOAR monomer “b.” Right inset: NMR structure of a STIM1 CC1α3-CC2 dimer. The STIM1 CC1α3-CC2 monomers kink between the 2 coiled-coil domains and form dimers via coupling in an antiparallel manner. C: hypothetical model of STIM1 in the resting state.
Mentions: STIM proteins (Fig. 1) are single TM proteins with an NH2-terminal portion including the Ca2+-sensing domain localized within the ER lumen and a long cytosolic strand, which couples to Orai channels in the PM. The STIM NH2 and COOH termini are separated by an ∼20-amino acid (aa) TM region (18, 84, 137) (Fig. 1A). The NH2-terminal portion is well conserved from worms and flies to humans, while the COOH-terminal portions are rather divergent among different species (20). The variety of STIM proteins is further extended by diverse splice variants like STIM1L (30) and a STIM2 splice variant (STIM2β, STIM2.1) (104, 136).

Bottom Line: Functional as well as mutagenesis studies together with structural insights about STIM and Orai proteins provide a molecular picture of the interplay of these two key players in the CRAC signaling cascade.This review focuses on the main experimental advances in the understanding of the STIM1-Orai choreography, thereby establishing a portrait of key mechanistic steps in the CRAC channel signaling cascade.The focus is on the activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and the consequent structural rearrangements that gate the Orai channels into the open state to allow Ca(2+)permeation into the cell.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics, Johannes Kepler University of Linz, Linz, Austria; and.

No MeSH data available.