- EMDB-13789: Structure of the human CPLANE complex -
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Entry
Database: EMDB / ID: EMD-13789
Title
Structure of the human CPLANE complex
Map data
Full map
Sample
Complex: CPLANE
Protein or peptide: WD repeat-containing and planar cell polarity effector protein fritz homolog
Protein or peptide: Protein inturned
Protein or peptide: Protein fuzzy homolog
Keywords
ciliogenesis / ciliopathies / longin / lipid binding / PROTEIN TRANSPORT
Function / homology
Function and homology information
negative regulation of neural crest formation / negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation / axonemal basal plate / tongue morphogenesis / respiratory system development / auditory receptor cell morphogenesis / regulation of embryonic cell shape / septin cytoskeleton organization / digestive system development / embryonic body morphogenesis ...negative regulation of neural crest formation / negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation / axonemal basal plate / tongue morphogenesis / respiratory system development / auditory receptor cell morphogenesis / regulation of embryonic cell shape / septin cytoskeleton organization / digestive system development / embryonic body morphogenesis / regulation of ruffle assembly / regulation of fibroblast migration / podocyte cell migration / establishment of planar polarity / protein localization to organelle / intraciliary transport / spinal cord dorsal/ventral patterning / regulation of cilium assembly / ciliary transition zone / motile cilium assembly / cilium organization / embryonic skeletal system morphogenesis / negative regulation of cell division / circulatory system development / positive regulation of cilium assembly / non-motile cilium assembly / camera-type eye development / regulation of smoothened signaling pathway / positive regulation of smoothened signaling pathway / limb development / neural tube development / motile cilium / regulation of establishment of cell polarity / regulation of focal adhesion assembly / hair follicle morphogenesis / embryonic digit morphogenesis / smoothened signaling pathway / roof of mouth development / axoneme / cilium assembly / hair follicle development / regulation of ossification / negative regulation of keratinocyte proliferation / Hedgehog 'off' state / keratinocyte differentiation / vesicle-mediated transport / centriole / phosphatidylinositol binding / ciliary basal body / negative regulation of cell migration / kidney development / neural tube closure / establishment of protein localization / negative regulation of canonical Wnt signaling pathway / cilium / protein transport / regulation of protein localization / nervous system development / cytoskeleton / cell division / negative regulation of cell population proliferation / cell surface / extracellular exosome / plasma membrane / cytoplasm Similarity search - Function
WD repeat-containing and planar cell polarity effector protein Fritz / Fuzzy protein / Protein inturned / WD repeat-containing and planar cell polarity effector protein Fritz / CCZ1/INTU, second Longin domain / CCZ1/INTU/HPS4, third Longin domain / Intu longin-like domain 2 / Intu longin-like domain 3 / CCZ1/INTU/HSP4, first Longin domain / First Longin domain of INTU, CCZ1 and HPS4 ...WD repeat-containing and planar cell polarity effector protein Fritz / Fuzzy protein / Protein inturned / WD repeat-containing and planar cell polarity effector protein Fritz / CCZ1/INTU, second Longin domain / CCZ1/INTU/HPS4, third Longin domain / Intu longin-like domain 2 / Intu longin-like domain 3 / CCZ1/INTU/HSP4, first Longin domain / First Longin domain of INTU, CCZ1 and HPS4 / FUZ/MON1/HPS1, third Longin domain / FUZ/MON1/HPS1, second Longin domain / FUZ/MON1/HPS1, first Longin domain / First Longin domain of FUZ, MON1 and HPS1 / Second Longin domain of FUZ, MON1 and HPS1 / Third Longin domain of FUZ, MON1 and HPS1 / PDZ domain profile. / Domain present in PSD-95, Dlg, and ZO-1/2. / PDZ domain / PDZ superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily Similarity search - Domain/homology
WD repeat-containing and planar cell polarity effector protein fritz homolog / Protein fuzzy homolog / Protein inturned Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.35 Å
Journal: Sci Adv / Year: 2022 Title: Structure of the ciliogenesis-associated CPLANE complex. Authors: Gerasimos Langousis / Simone Cavadini / Niels Boegholm / Esben Lorentzen / Georg Kempf / Patrick Matthias / Abstract: Dysfunctional cilia cause pleiotropic human diseases termed ciliopathies. These hereditary maladies are often caused by defects in cilia assembly, a complex event that is regulated by the ...Dysfunctional cilia cause pleiotropic human diseases termed ciliopathies. These hereditary maladies are often caused by defects in cilia assembly, a complex event that is regulated by the ciliogenesis and planar polarity effector (CPLANE) proteins Wdpcp, Inturned, and Fuzzy. CPLANE proteins are essential for building the cilium and are mutated in multiple ciliopathies, yet their structure and molecular functions remain elusive. Here, we show that mammalian CPLANE proteins comprise a bona fide complex and report the near-atomic resolution structures of the human Wdpcp-Inturned-Fuzzy complex and of the mouse Wdpcp-Inturned-Fuzzy complex bound to the small guanosine triphosphatase Rsg1. Notably, the crescent-shaped CPLANE complex binds phospholipids such as phosphatidylinositol 3-phosphate via multiple modules and a CPLANE ciliopathy mutant exhibits aberrant lipid binding. Our study provides critical structural and functional insights into an enigmatic ciliogenesis-associated complex as well as unexpected molecular rationales for ciliopathies.
Macromolecule #1: WD repeat-containing and planar cell polarity effector protein fr...
Macromolecule
Name: WD repeat-containing and planar cell polarity effector protein fritz homolog type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
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