7d7e

From Proteopedia

Jump to: navigation, search

Structure of PKD1L3-CTD/PKD2L1 in apo state

Structural highlights

7d7e is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.4Å
Ligands:CA, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The heteromeric complex between PKD1L3, a member of the polycystic kidney disease (PKD) protein family, and PKD2L1, also known as TRPP2 or TRPP3, has been a prototype for mechanistic characterization of heterotetrametric TRP-like channels. Here we show that a truncated PKD1L3/PKD2L1 complex with the C-terminal TRP-fold fragment of PKD1L3 retains both Ca(2+) and acid-induced channel activities. Cryo-EM structures of this core heterocomplex with or without supplemented Ca(2+) were determined at resolutions of 3.1 A and 3.4 A, respectively. The heterotetramer, with a pseudo-symmetric TRP architecture of 1:3 stoichiometry, has an asymmetric selectivity filter (SF) guarded by Lys2069 from PKD1L3 and Asp523 from the three PKD2L1 subunits. Ca(2+)-entrance to the SF vestibule is accompanied by a swing motion of Lys2069 on PKD1L3. The S6 of PKD1L3 is pushed inward by the S4-S5 linker of the nearby PKD2L1 (PKD2L1-III), resulting in an elongated intracellular gate which seals the pore domain. Comparison of the apo and Ca(2+)-loaded complexes unveils an unprecedented Ca(2+) binding site in the extracellular cleft of the voltage-sensing domain (VSD) of PKD2L1-III, but not the other three VSDs. Structure-guided mutagenic studies support this unconventional site to be responsible for Ca(2+)-induced channel activation through an allosteric mechanism.

Structural basis for Ca(2+) activation of the heteromeric PKD1L3/PKD2L1 channel.,Su Q, Chen M, Wang Y, Li B, Jing D, Zhan X, Yu Y, Shi Y Nat Commun. 2021 Aug 11;12(1):4871. doi: 10.1038/s41467-021-25216-z. PMID:34381056[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
3 reviews cite this structure
TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.
Zhang et al. (2023)
2 more
6 other articles
No citations found

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ Su Q, Chen M, Wang Y, Li B, Jing D, Zhan X, Yu Y, Shi Y. Structural basis for Ca(2+) activation of the heteromeric PKD1L3/PKD2L1 channel. Nat Commun. 2021 Aug 11;12(1):4871. PMID:34381056 doi:10.1038/s41467-021-25216-z

Contents


PDB ID 7d7e

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/7d7e"
Personal tools