Title : Structural basis for
receptor recognition of vitamin-B(12)-
intrinsic factor complexes
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
Output (sent_index, trigger,
protein,
sugar,
site):
- 5. domains, , -, a Ca(2+)-dependent manner, -
Output(Part-Of) (sent_index,
protein,
site):
- 5. Cbl, domains
- 5. Cbl, regions
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):