Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1

Molland, Katrina L.; Paul, Lake N.; Yernool, Dinesh

doi:10.1016/j.bbapap.2011.12.002

Cited by 12 publications

(15 citation statements)

References 35 publications

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“…5e). The TRPP3 coiled-coil trimer structure reported here is virtually identical to a recently released crystal structure of a similar TRPP3 region 34 .…”

Section: Resultssupporting

confidence: 82%

Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

Ulbrich

et al. 2012

Nat Commun

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Polycystic kidney disease (PKD) family proteins associate with transient receptor potential (TRP) channel family proteins to form functionally important complexes. PKD proteins differ from known ion channel-forming proteins and are generally thought to act as membrane receptors. Here we find that PKD1L3, a PKD protein, functions as a channel-forming subunit in an acid-sensing heteromeric complex formed by PKD1L3 and TRPP3, a TRP channel protein. Single amino acid mutations in the putative pore region of both proteins alter the channel's ion selectivity. The PKD1L3/TRPP3 complex in the plasma membrane of live cells contains one PKD1L3 and three TRPP3. A TRPP3 C-terminal coiled-coil domain forms a trimer in solution and in crystal and plays a crucial role in the assembly and surface expression of the PKD1L3/TRPP3 complex. These results demonstrate that PKD subunits constitute a new class of channel-forming proteins, enriching our understanding of the function of PKD proteins and PKD/TRPP complexes.

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“…5e). The TRPP3 coiled-coil trimer structure reported here is virtually identical to a recently released crystal structure of a similar TRPP3 region 34 .…”

Section: Resultssupporting

confidence: 82%

Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

Ulbrich

et al. 2012

Nat Commun

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“…Interestingly, under the reducing condition, a significant portion of trimers remained while all tetramers and the majority of dimers were absent. These data indicated that the oligomerization strength follows an order of trimer ≫ dimer > tetramer, consistent with a previous finding that the PKD2L1 CT forms very stable trimers in vitro 22 23 .…”

Section: Resultssupporting

confidence: 92%

“…Previous studies on PKD2L1 oligomerization were limited to in vitro conditions, including trimerization of its purified C-terminus or of the full-length protein over-expressed in Xenopus oocytes 21 22 23 . In order to determine the oligomeric states of PKD2L1 under more in vivo and physiological conditions, we performed Western Blot (WB) experiments using mouse tissues under the non-reducing and reducing conditions (see EXPERIMENTAL PROCEDURES).…”

Section: Resultsmentioning

confidence: 99%

“…Although no corresponding information for PKD2L1/PKD1 and PKD2L1/PKD1L1 is available it is reasonable to speculate that they are also organized with the same stoichiometry. The PKD2L1 C-terminal coiled-coil 2 domain (CC2, G699-W743) was found to homotrimerize in vitro and be important for PKD2L1 homomeric assembly and PKD2L1/PKD1L3 surface expression in Xenopus oocytes 21 22 23 . However, a previous study found that PKD2L1 truncation mutants lacking CC2 possess similar Ca 2+ -activated channel function as wild-type (WT) PKD2L1 and that PKD2L1 and PKD1L3 interact with each other through their TMs, which is required for PKD2L1/PKD1L3 surface expression in HEK cells 24 .…”

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confidence: 99%

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A novel PKD2L1 C-terminal domain critical for trimerization and channel function

Zheng

Hussein

Yang

et al. 2015

Sci Rep

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As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

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“…X-ray structures of the TRPP2 and TRPP3 C-terminal coiled coils have been determined (Molland et al, 2012; Yu et al, 2009; Yu et al, 2012). Consistent with the heteromeric assemblies described above, the coiled coils of TRPP2 and TRPP3 form stable parallel trimers.…”

Section: Structural Information On Trp Channelsmentioning

confidence: 99%

Structural Biology of TRP Channels

Hellmich

Gaudet

2014

Handbook of Experimental Pharmacology

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Membrane proteins remain challenging targets for structural biologists, despite recent technical developments regarding sample preparation and structure determination. We review recent progress towards a structural understanding of TRP channels and the techniques used to that end. We discuss available low-resolution structures from electron microscopy (EM), X-ray crystallography and nuclear magnetic resonance (NMR), and review the resulting insights into TRP channel function for various subfamily members. The recent high-resolution structure of TRPV1 is discussed in more detail in Chapter X. We also consider the opportunities and challenges of using the accumulating structural information on TRPs and homologous proteins for deducing full-length structures of different TRP channel subfamilies, such as building homology models. Finally, we close by summarizing the outlook of the “holy grail” of understanding in atomic detail the diverse functions of TRP channels.

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Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1

Cited by 12 publications

References 35 publications

Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex

A novel PKD2L1 C-terminal domain critical for trimerization and channel function

Structural Biology of TRP Channels

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