B12- asiaa .Ohutsuolireseptori CUBN joka tunnistaa IF-Cbl kompleksia

IF-Cbl kompleksin reseptori CUB

https://www.ncbi.nlm.nih.gov/pubmed/20237569

Nature. 2010 Mar 18;464(7287):445-8. doi: 10.1038/nature08874.

Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.

Andersen CB¹, Madsen M, Storm T, Moestrup SK, Andersen GR.

Abstract

Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin and the 45-kDa transmembrane protein amnionless. Loss of function of any of these proteins ultimately leads to Cbl deficiency in man. Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution. The structure provides insight into how several CUB (for 'complement C1r/C1s, Uegf, Bmp1') domains collectively function as modular ligand-binding regions, and how two distant CUB domains embrace the Cbl molecule by binding the two IF domains in a Ca(2+)-dependent manner.
This dual-point model provides a probable explanation of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca(2+)-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca(2+)-coordinating acidic aspartates/glutamates is a common theme of Ca(2+)-dependent ligand-receptor interactions.

PMID:

20237569

DOI:

10.1038/nature08874

[Indexed for MEDLINE]

IF-B12- kompleksin reseptori 

Geeni  CUBN Kr.10p12. 

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.
2. The CUBN haplotypes were associated with an altered gastric cancer risk.
3. CUBN was associated with albuminuria in type 2 diabetes patients.
4. The variant rs11254363 of the CUBN gene was associated with a decreased risk of developing congenital heart disease in Han Chinese populations
5. MA is associated with CVD irrespective of the presence of the CUBN risk allele. These results challenge the concept that albuminuria in the setting of this mutation is benign.
6. Cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apolipoprotein (apo)A-I, significantly increasing urinary loss of albumin and apoA-I.
7. predisposition to multibacillary leprosy in Vietnam is associated with CUBN and NEBL common variants in the chromosome 10p13 linkage region
8. LOS treatment decreased microalbuminuria induced by Cd apparently through a cubilin receptor-dependent mechanism but independent of megalin.
9. Data suggest that endodermal layer of yolk sac and syncytiotrophoblast/cytotrophoblast cells of placental villi express cubilin mRNA/protein; expression of cubilin mRNA/protein is up-regulated as gestation/placentation progresses.
10. The p.I1e2984Val variant of cubulin is part of a larger haplotype in European populations that is almost absent in West Africans.

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