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[摘要]：Mannan-binding lectin (MBL) is a soluble, collagen-like C-type lectin that shows the ability to bind certain N-glycosylated carbohydrates through calcium-dependent CRDs. It is composed of three identical polypeptides that form a helical homotrimer further arranged in octadecameric and larger oligomers with a very complex quaternary structure. Several studies have revealed that this protein modulates the immune response, being able to mediate phagocytosis. Unsuitable for industrial-scale production, due to the costs and the difficulties inherent in its extremely complex quaternary structure, its potential for use in successful anti-infective therapy is limited. To produce better, less expensive therapeutic agents, less complex chimeric fusion proteins with similar ligand recognition and enhanced effector functions have been developed. In a previous study, recombinant human MBL (rhMBL) and three L-ficolin (L-FCN) variants containing the MBL carbohydrate recognition domain and varying lengths of the collagenous domain with potential clinical application against glycosylated enveloped viruses such as Ebola and Marburg were produced. It was also demonstrated that one of these chimeras L-FCN/MBL76 had superior effector activity that appeared to be mediated by greater structural flexibility. In this work we have used an NMR-based approach to study, at the atomic level, the mannose-binding activities both of rhMBL and of the chimeric molecule L-FCN/MBL76. Our findings indicate that the analysis of the binding dynamics of immune effector molecules could be useful for the design and optimization of new therapeutic proteins. |
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