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PDBsum entry 5dse
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Protein binding
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PDB id
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5dse
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Contents |
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537 a.a.
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231 a.a.
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712 a.a.
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264 a.a.
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PDB id:
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| Name: |
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Protein binding
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Title:
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Crystal structure of the ttc7b/hyccin complex
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Structure:
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Tetratricopeptide repeat protein 7b. Chain: a, c. Synonym: tpr repeat protein 7b,tetratricopeptide repeat protein 7- like-1,tpr repeat protein 7-like-1. Engineered: yes. Hyccin. Chain: b, d. Synonym: down-regulated by ctnnb1 protein a,protein fam126a. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ttc7b, ttc7l1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: fam126a, drctnnb1a.
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Resolution:
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2.90Å
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R-factor:
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0.213
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R-free:
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0.242
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Authors:
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X.Wu,J.M.Baskin,K.M.Reinisch,P.De Camilli
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Key ref:
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J.M.Baskin
et al.
(2016).
The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane.
Nat Cell Biol,
18,
132-138.
PubMed id:
DOI:
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Date:
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17-Sep-15
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Release date:
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02-Dec-15
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PROCHECK
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Headers
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References
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Q86TV6
(TTC7B_HUMAN) -
Tetratricopeptide repeat protein 7B from Homo sapiens
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Seq:
Struc:
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843 a.a.
537 a.a.
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Q9BYI3
(HYCCI_HUMAN) -
Hyccin from Homo sapiens
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Seq:
Struc:
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521 a.a.
231 a.a.
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DOI no:
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Nat Cell Biol
18:132-138
(2016)
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PubMed id:
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The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane.
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J.M.Baskin,
X.Wu,
R.Christiano,
M.S.Oh,
C.M.Schauder,
E.Gazzerro,
M.Messa,
S.Baldassari,
S.Assereto,
R.Biancheri,
F.Zara,
C.Minetti,
A.Raimondi,
M.Simons,
T.C.Walther,
K.M.Reinisch,
P.De Camilli.
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ABSTRACT
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Genetic defects in myelin formation and maintenance cause leukodystrophies, a
group of white matter diseases whose mechanistic underpinnings are poorly
understood. Hypomyelination and congenital cataract (HCC), one of these
disorders, is caused by mutations in FAM126A, a gene of unknown function. We
show that FAM126A, also known as hyccin, regulates the synthesis of
phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane
identity. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is
an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase
complex that comprises PI4KIIIα and its adaptors TTC7 and EFR3 (refs ,). A
FAM126A-TTC7 co-crystal structure reveals an all-α-helical heterodimer with a
large protein-protein interface and a conserved surface that may mediate binding
to PI4KIIIα. Absence of FAM126A, the predominant FAM126 isoform in
oligodendrocytes, destabilizes the PI4KIIIα complex in mouse brain and patient
fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P
production in oligodendrocytes, whose specialized function requires massive
plasma membrane expansion and thus generation of PtdIns(4)P and downstream
phosphoinositides. Our results point to a role for FAM126A in supporting
myelination, an important process in development and also following acute
exacerbations in multiple sclerosis.
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