Unknown

Dataset Information

0

Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry.


ABSTRACT: Stromal interaction molecules (STIM)s function as endoplasmic reticulum calcium (Ca(2+)) sensors that differentially regulate plasma membrane Ca(2+) release activated Ca(2+) channels in various cells. To probe the structural basis for the functional differences between STIM1 and STIM2 we engineered a series of EF-hand and sterile ? motif (SAM) domain (EF-SAM) chimeras, demonstrating that the STIM1 Ca(2+)-binding EF-hand and the STIM2 SAM domain are major contributors to the autoinhibition of oligomerization in each respective isoform. Our nuclear magnetic resonance (NMR) derived STIM2 EF-SAM structure provides a rationale for an augmented stability, which involves a 54° pivot in the EF-hand:SAM domain orientation permissible by an expanded nonpolar cleft, ionic interactions, and an enhanced hydrophobic SAM core, unique to STIM2. Live cells expressing "super-unstable" or "super-stable" STIM1/STIM2 EF-SAM chimeras in the full-length context show a remarkable correlation with the in vitro data. Together, our data suggest that divergent Ca(2+)- and SAM-dependent stabilization of the EF-SAM fold contributes to the disparate regulation of store-operated Ca(2+) entry by STIM1 and STIM2.

SUBMITTER: Zheng L 

PROVIDER: S-EPMC3029719 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry.

Zheng Le L   Stathopulos Peter B PB   Schindl Rainer R   Li Guang-Yao GY   Romanin Christoph C   Ikura Mitsuhiko M  

Proceedings of the National Academy of Sciences of the United States of America 20110107 4


Stromal interaction molecules (STIM)s function as endoplasmic reticulum calcium (Ca(2+)) sensors that differentially regulate plasma membrane Ca(2+) release activated Ca(2+) channels in various cells. To probe the structural basis for the functional differences between STIM1 and STIM2 we engineered a series of EF-hand and sterile α motif (SAM) domain (EF-SAM) chimeras, demonstrating that the STIM1 Ca(2+)-binding EF-hand and the STIM2 SAM domain are major contributors to the autoinhibition of oli  ...[more]

Similar Datasets

| S-EPMC6462238 | biostudies-literature
| S-EPMC5955777 | biostudies-literature
| S-EPMC6461473 | biostudies-literature
| S-EPMC5561850 | biostudies-other
| S-EPMC5777820 | biostudies-literature
| S-EPMC4329424 | biostudies-literature
| S-EPMC4411291 | biostudies-literature
| S-EPMC3593819 | biostudies-literature
| S-EPMC4926963 | biostudies-literature
| S-EPMC2267267 | biostudies-other