| Structural highlights
Function
[PK2L1_MOUSE] Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect. May play a role in the perception of carbonation taste.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 A resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of pi-pi interactions, suggesting a potential PKD2L1 gating mechanism.
Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.,Su Q, Hu F, Liu Y, Ge X, Mei C, Yu S, Shen A, Zhou Q, Yan C, Lei J, Zhang Y, Liu X, Wang T Nat Commun. 2018 Mar 22;9(1):1192. doi: 10.1038/s41467-018-03606-0. PMID:29567962[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murakami M, Ohba T, Xu F, Shida S, Satoh E, Ono K, Miyoshi I, Watanabe H, Ito H, Iijima T. Genomic organization and functional analysis of murine PKD2L1. J Biol Chem. 2005 Feb 18;280(7):5626-35. doi: 10.1074/jbc.M411496200. Epub 2004, Nov 17. PMID:15548533 doi:http://dx.doi.org/10.1074/jbc.M411496200
- ↑ Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H. Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12569-74. doi:, 10.1073/pnas.0602702103. Epub 2006 Aug 4. PMID:16891422 doi:http://dx.doi.org/10.1073/pnas.0602702103
- ↑ Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS. The cells and logic for mammalian sour taste detection. Nature. 2006 Aug 24;442(7105):934-8. doi: 10.1038/nature05084. PMID:16929298 doi:http://dx.doi.org/10.1038/nature05084
- ↑ Chandrashekar J, Yarmolinsky D, von Buchholtz L, Oka Y, Sly W, Ryba NJ, Zuker CS. The taste of carbonation. Science. 2009 Oct 16;326(5951):443-5. doi: 10.1126/science.1174601. PMID:19833970 doi:http://dx.doi.org/10.1126/science.1174601
- ↑ Chang RB, Waters H, Liman ER. A proton current drives action potentials in genetically identified sour taste cells. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22320-5. doi:, 10.1073/pnas.1013664107. Epub 2010 Nov 23. PMID:21098668 doi:http://dx.doi.org/10.1073/pnas.1013664107
- ↑ Horio N, Yoshida R, Yasumatsu K, Yanagawa Y, Ishimaru Y, Matsunami H, Ninomiya Y. Sour taste responses in mice lacking PKD channels. PLoS One. 2011;6(5):e20007. doi: 10.1371/journal.pone.0020007. Epub 2011 May 19. PMID:21625513 doi:http://dx.doi.org/10.1371/journal.pone.0020007
- ↑ Delling M, DeCaen PG, Doerner JF, Febvay S, Clapham DE. Primary cilia are specialized calcium signalling organelles. Nature. 2013 Dec 12;504(7479):311-4. doi: 10.1038/nature12833. PMID:24336288 doi:http://dx.doi.org/10.1038/nature12833
- ↑ DeCaen PG, Delling M, Vien TN, Clapham DE. Direct recording and molecular identification of the calcium channel of primary cilia. Nature. 2013 Dec 12;504(7479):315-8. doi: 10.1038/nature12832. PMID:24336289 doi:http://dx.doi.org/10.1038/nature12832
- ↑ Su Q, Hu F, Liu Y, Ge X, Mei C, Yu S, Shen A, Zhou Q, Yan C, Lei J, Zhang Y, Liu X, Wang T. Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1. Nat Commun. 2018 Mar 22;9(1):1192. doi: 10.1038/s41467-018-03606-0. PMID:29567962 doi:http://dx.doi.org/10.1038/s41467-018-03606-0
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