PMID: 16407218

 

    Legend: Gene, Sites

Title : Interaction of mannan binding lectin with alpha2 macroglobulin via exposed oligomannose glycans: a conserved feature of the thiol ester protein family

Abstract :
  1. The serum col lectin mannan-binding lectin ( MBL ) binds to oligomannose and GlcNAc-terminating glycans present on microorganisms
  2. Using a commercial affinity chromatography resin containing immobilized MBL we screened human and mouse serum for endogenous MBL-binding targets
  3. We isolated the serum protease inhibitor alpha(2) macroglobulin ( alpha2M ), a heavily glycosylated thiol ester protein ( TEP ) composed of four identical 180-kDa subunits , each of which has eight N-linked glycosylation sites
  4. alpha2M has previously been reported to interact with MBL ; however, the interaction was not characterized
  5. We investigated the mechanism of formation of complexes between alpha2M and MBL and concluded that they form by the direct binding of oligomannose glycans Man(5-7) occupying Asn-846 on alpha2M to the lectin domains (carbohydrate recognition domains) of MBL
  6. The oligomannose glycans are accessible for lectin binding on both active alpha2M (thiol ester intact) and protease-cleaved alpha2M (thiol ester cleaved)
  7. We demonstrate that MBL is able to interact with alpha2M in the fluid phase, but the interaction does not inhibit the binding of MBL to mannan-coated surfaces
  8. In addition to alpha2M , two other members of the TEP family, C3 and C4, which also contain oligomannose glycans, were captured from human serum using the MBL resin
  9. MBL binding may be a conserved feature of the TEPs, dating from their ancestral origins
  10. We suggest that the inhibition of proteases on the surface of microorganisms by an ancestral alpha2M-like TEP may generate "arrays" of oligomannose glycans to which MBL or other lectins can bind
  11. Binding would lead to opsonization or activation of enzyme systems such as complement
Output (sent_index, trigger, protein, sugar, site):
  • 3. glycosylated, , TEP, -, -
  • 3. glycosylated, , alpha(2) macroglobulin, -, -
  • 3. glycosylated, , protein, -, -
  • 3. glycosylation, , -, -, sites
  • 5. MBL, , MBL, carbohydrate recognition domains, -
  • 5. lectin, , lectin, carbohydrate recognition domains, -
Output(Part-Of) (sent_index, protein, site):
  • 3. subunits, sites
  • 5. MBL, domains
  • 5. alpha2M, Asn-846
  • 5. lectin, domains
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
MBL 4153 1,2,4,5,7,8,9,10
mannan binding lectin 4153 0