RGD Reference Report - Near-planar solution structures of mannose-binding lectin oligomers provide insight on activation of lectin pathway of complement. - Rat Genome Database

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Near-planar solution structures of mannose-binding lectin oligomers provide insight on activation of lectin pathway of complement.

Authors: Miller, A  Phillips, A  Gor, J  Wallis, R  Perkins, SJ 
Citation: Miller A, etal., J Biol Chem. 2012 Feb 3;287(6):3930-45. doi: 10.1074/jbc.M111.320341. Epub 2011 Dec 13.
RGD ID: 7247590
Pubmed: PMID:22167201   (View Abstract at PubMed)
PMCID: PMC3281675   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.320341   (Journal Full-text)

The complement system is a fundamental component of innate immunity that orchestrates complex immunological and inflammatory processes. Complement comprises over 30 proteins that eliminate invading microorganisms while maintaining host cell integrity. Protein-carbohydrate interactions play critical roles in both the activation and regulation of complement. Mannose-binding lectin (MBL) activates the lectin pathway of complement via the recognition of sugar arrays on pathogenic surfaces. To determine the solution structure of MBL, synchrotron x-ray scattering and analytical ultracentrifugation experiments showed that the carbohydrate-recognition domains in the MBL dimer, trimer, and tetramer are positioned close to each other in near-planar fan-like structures. These data were subjected to constrained modeling fits. A bent structure for the MBL monomer was identified starting from two crystal structures for its carbohydrate-recognition domain and its triple helical region. The MBL monomer structure was used to identify 10-12 near-planar solution structures for each of the MBL dimers, trimers, and tetramers starting from 900 to 6,859 randomized structures for each. These near-planar fan-like solution structures joined at an N-terminal hub clarified how the carbohydrate-recognition domain of MBL binds to pathogenic surfaces. They also provided insight on how MBL presents a structural template for the binding and auto-activation of the MBL-associated serine proteases to initiate the lectin pathway of complement activation.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mbl1RatD-mannose binding  IDA  RGD 
Mbl1Ratidentical protein binding  IPIMbl1 (Rattus norvegicus)homodimerization and homotrimerization and homotetramerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mbl1  (mannose binding lectin 1)


Additional Information