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PDBsum entry 3kq4

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protein ligands metals Protein-protein interface(s) links
Transport protein PDB id
3kq4
Jmol
Contents
Protein chains
385 a.a. *
457 a.a. *
Ligands
NAG ×21
NAG-NAG-BMA-MAN-
MAN
×6
B12 ×3
NAG-NAG ×3
Metals
_CA ×12
* Residue conservation analysis
PDB id:
3kq4
Name: Transport protein
Title: Structure of intrinsic factor-cobalamin bound to its recepto
Structure: Gastric intrinsic factor. Chain: a, c, e. Fragment: unp residues 25-417. Synonym: intrinsic factor, inf, if. Engineered: yes. Cubilin. Chain: b, d, f. Fragment: unp residues 932-1388. Synonym: intrinsic factor-cobalamin receptor, intrinsic fac
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gif, ifmh. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Gene: cubn, ifcr. Expressed in: cricetulus griseus. Expression_system_taxid: 10029
Resolution:
3.30Å     R-factor:   0.211     R-free:   0.242
Authors: C.B.F.Andersen,M.Madsen,S.K.Moestrup,G.R.Andersen
Key ref: C.B.Andersen et al. (2010). Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. Nature, 464, 445-448. PubMed id: 20237569
Date:
17-Nov-09     Release date:   09-Mar-10    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P27352  (IF_HUMAN) -  Gastric intrinsic factor
Seq:
Struc:
417 a.a.
385 a.a.*
Protein chains
Pfam   ArchSchema ?
O60494  (CUBN_HUMAN) -  Cubilin
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
3623 a.a.
457 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   7 terms 
  Biological process     small molecule metabolic process   9 terms 
  Biochemical function     cobalamin binding     2 terms  

 

 
Nature 464:445-448 (2010)
PubMed id: 20237569  
 
 
Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.
C.B.Andersen, M.Madsen, T.Storm, S.K.Moestrup, G.R.Andersen.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21312325 D.Watkins, and D.S.Rosenblatt (2011).
Inborn errors of cobalamin absorption and metabolism.
  Am J Med Genet C Semin Med Genet, 157, 33-44.  
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