PMID- 23816623
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20211021
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 202
IP  - 1
DP  - 2013 Jul 8
TI  - The STIM1 CTID domain determines access of SARAF to SOAR to regulate Orai1 
      channel function.
PG  - 71-9
LID - 10.1083/jcb.201301148 [doi]
AB  - Ca(2+) influx by store-operated Ca(2+) channels (SOCs) mediates all 
      Ca(2+)-dependent cell functions, but excess Ca(2+) influx is highly toxic. The 
      molecular components of SOC are the pore-forming Orai1 channel and the 
      endoplasmic reticulum Ca(2+) sensor STIM1. Slow Ca(2+)-dependent inactivation 
      (SCDI) of Orai1 guards against cell damage, but its molecular mechanism is 
      unknown. Here, we used homology modeling to identify a conserved STIM1(448-530) 
      C-terminal inhibitory domain (CTID), whose deletion resulted in spontaneous 
      clustering of STIM1 and full activation of Orai1 in the absence of store 
      depletion. CTID regulated SCDI by determining access to and interaction of the 
      STIM1 inhibitor SARAF with STIM1 Orai1 activation region (SOAR), the STIM1 domain 
      that activates Orai1. CTID had two lobes, STIM1(448-490) and STIM1(490-530), with 
      distinct roles in mediating access of SARAF to SOAR. The STIM1(448-490) lobe 
      restricted, whereas the STIM1(490-530) lobe directed, SARAF to SOAR. The two 
      lobes cooperated to determine the features of SCDI. These findings highlight the 
      central role of STIM1 in SCDI and provide a molecular mechanism for SCDI of 
      Orai1.
FAU - Jha, Archana
AU  - Jha A
AD  - Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics 
      Branch, National Institute of Dental and Craniofacial Research, National 
      Institutes of Health, Bethesda, MD 20892, USA.
FAU - Ahuja, Malini
AU  - Ahuja M
FAU - Maleth, Jozsef
AU  - Maleth J
FAU - Moreno, Claudia M
AU  - Moreno CM
FAU - Yuan, Joseph P
AU  - Yuan JP
FAU - Kim, Min Seuk
AU  - Kim MS
FAU - Muallem, Shmuel
AU  - Muallem S
LA  - eng
GR  - ZIA DE000735/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20130701
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Calcium Channels)
RN  - 0 (Intracellular Calcium-Sensing Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (ORAI1 Protein)
RN  - 0 (ORAI1 protein, human)
RN  - 0 (SARAF protein, human)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Calcium/metabolism
MH  - Calcium Channels/genetics/*metabolism
MH  - Cell Membrane/genetics/metabolism
MH  - Conserved Sequence
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Calcium-Sensing Proteins
MH  - Membrane Proteins/genetics/*metabolism
MH  - Models, Molecular
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - ORAI1 Protein
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Interaction Mapping
MH  - Protein Structure, Tertiary
MH  - Sequence Deletion
MH  - Stromal Interaction Molecule 1
MH  - Structural Homology, Protein
MH  - Structure-Activity Relationship
PMC - PMC3704993
EDAT- 2013/07/03 06:00
MHDA- 2013/09/10 06:00
PMCR- 2014/01/08
CRDT- 2013/07/03 06:00
PHST- 2013/07/03 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
PHST- 2014/01/08 00:00 [pmc-release]
AID - jcb.201301148 [pii]
AID - 201301148 [pii]
AID - 10.1083/jcb.201301148 [doi]
PST - ppublish
SO  - J Cell Biol. 2013 Jul 8;202(1):71-9. doi: 10.1083/jcb.201301148. Epub 2013 Jul 1.