Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2009 Jul 14;10628:11558-63. doi: 10.1073/pnas.0903684106.
Show Gene links
Show Anatomy links
Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.
Yu Y
,
Ulbrich MH
,
Li MH
,
Buraei Z
,
Chen XZ
,
Ong AC
,
Tong L
,
Isacoff EY
,
Yang J
.
???displayArticle.abstract???
Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations.
Babich,
The N-terminal extracellular domain is required for polycystin-1-dependent channel activity.
2004, Pubmed
Babich,
The N-terminal extracellular domain is required for polycystin-1-dependent channel activity.
2004,
Pubmed
Bai,
Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits.
2008,
Pubmed
Celić,
Domain mapping of the polycystin-2 C-terminal tail using de novo molecular modeling and biophysical analysis.
2008,
Pubmed
Cheng,
Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties.
2007,
Pubmed
Delmas,
Gating of the polycystin ion channel signaling complex in neurons and kidney cells.
2004,
Pubmed
Delmas,
Polycystins: polymodal receptor/ion-channel cellular sensors.
2005,
Pubmed
Feng,
Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2.
2008,
Pubmed
Fujiwara,
X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil.
2008,
Pubmed
Giamarchi,
The versatile nature of the calcium-permeable cation channel TRPP2.
2006,
Pubmed
González-Perrett,
Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel.
2001,
Pubmed
Grimm,
Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells.
2003,
Pubmed
Hanaoka,
Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
,
Pubmed
Harris,
Polycystic kidney disease.
2009,
Pubmed
Hoenderop,
Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6.
2003,
Pubmed
,
Xenbase
Hughes,
The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains.
1995,
Pubmed
Koulen,
Polycystin-2 is an intracellular calcium release channel.
2002,
Pubmed
Köttgen,
TRPP2 and TRPV4 form a polymodal sensory channel complex.
2008,
Pubmed
Köttgen,
Subcellular localization and trafficking of polycystins.
2005,
Pubmed
Köttgen,
TRPP2 and autosomal dominant polycystic kidney disease.
2007,
Pubmed
Luo,
Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia.
2003,
Pubmed
,
Xenbase
Lupas,
The structure of alpha-helical coiled coils.
2005,
Pubmed
Maroto,
TRPC1 forms the stretch-activated cation channel in vertebrate cells.
2005,
Pubmed
,
Xenbase
Matulef,
Cyclic nucleotide-gated ion channels.
2003,
Pubmed
Mio,
The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas.
2007,
Pubmed
Mochizuki,
PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein.
1996,
Pubmed
Nauli,
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.
2003,
Pubmed
Newby,
Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex.
2002,
Pubmed
Ong,
Molecular pathogenesis of ADPKD: the polycystin complex gets complex.
2005,
Pubmed
Parry,
Fifty years of coiled-coils and alpha-helical bundles: a close relationship between sequence and structure.
2008,
Pubmed
Qian,
PKD1 interacts with PKD2 through a probable coiled-coil domain.
1997,
Pubmed
Tsiokas,
Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
1997,
Pubmed
Tsiokas,
Specific association of the gene product of PKD2 with the TRPC1 channel.
1999,
Pubmed
Tsiokas,
Cell biology of polycystin-2.
2007,
Pubmed
Ulbrich,
Subunit counting in membrane-bound proteins.
2007,
Pubmed
,
Xenbase
Vassilev,
Polycystin-2 is a novel cation channel implicated in defective intracellular Ca(2+) homeostasis in polycystic kidney disease.
2001,
Pubmed
,
Xenbase
Weitz,
Subunit stoichiometry of the CNG channel of rod photoreceptors.
2002,
Pubmed
Woolfson,
The design of coiled-coil structures and assemblies.
2005,
Pubmed
Wu,
Molecular genetics and mechanism of autosomal dominant polycystic kidney disease.
2000,
Pubmed
Zhang,
The multimeric structure of polycystin-2 (TRPP2): structural-functional correlates of homo- and hetero-multimers with TRPC1.
2009,
Pubmed
Zheng,
Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit.
2002,
Pubmed
,
Xenbase
Zhong,
The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry.
2002,
Pubmed
Zhong,
Selective heteromeric assembly of cyclic nucleotide-gated channels.
2003,
Pubmed
