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Scientists Reveal Structure and Function of a Novel Family of TRIC Channels
Calcium ions (Ca2+), as an essential secondary messenger in cellular signal transduction pathways, take part in important cellular functions including muscle contraction, cell growth and cell death. Robust counter-ion currents are vital to balance potential across the SR/ER membrane and to maintain efficient Ca2+ release and re-uptake. Trimeric intracellular cation channels (TRICs) play an important role as counter-ion channels for balancing the charge potential change during Ca2+ release/uptake in the intracellular stores.
Recently, researchers led by Dr. CHEN Yuhang at Institute of Genetics and Development Biology (IGDB), Chinese Academy of Sciences, analyzed the structure and function of a novel family of TRIC channels, in collaboration with the scientists led by Dr. Wayne A. Hendrickson at New York Structural Biology Center/Columbia University (NYSBC/CU) and the scientists led by Dr. Andrew R. Marks at Columbia University (CU).
Bioinformatics analysis revealed that homologs of mammalian TRIC channels also distribute in bacteria, archaea and eukaryotes. The researchers from CHEN’s lab solved the structure of two prokaryotic homologs, achaeal SaTRIC at the resolution of 1.6 Å and bacterial CpTRIC at the resolution of 2.4 Å.
Their work demonstrated that TRIC channels belong to a novel class of cation channel, which are symmetrical trimers with transmembrane pores through each protomer. Each pore holds a string of water molecules centered at kinked helices in two inverted-repeat triple-helix bundles (THBs). The THB at one side in this structure is open and the THB at the other side locks the channel in a closed conformation. They also confirmed that prokaryotic TRICs have similar electrophysiological properties as those of mammalian TRICs.
This work further proposed a novel gating mechanism, which provides an excellent basis for understanding the biochemical properties of TRIC channels and their relevance to channel physiology.
“In mammals, TRIC channels have two isoforms with distinctive regulatory properties: TRIC-A is abundantly expressed in sarcoplasmic reticulum (SR) of excitable cells, while TRIC-B is expressed ubiquitously in endoplasmic reticulum (ER) of non-excitable cells. Mutations in TRIC-A have been linked to hypertension and muscular diseases, whereas mutations in TRIC-B have been linked to bone and pulmonary diseases.” Dr. CHEN said, “The structural and functional analyses of TRIC channels will provide the scientific basis to demonstrate the pathology of these related diseases.”
Their research results titled “Structural Basis for Conductance through TRIC Cation Channels” was published in Nature Communications (DOI:10.1038/ncomms15103), On May 19th.
This work is financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB08020301), the National 973 Project Grant of the Ministry of Science and Technology (2015CB910102,2016YFA0500503), the National Natural Science Foundation (31322005), and the National Thousand Young Talents program.
Structural and functional analyses of a novel family of TRIC channels. (Image by IGDB)
Dr. CHEN Yuhang