Mannan-Binding Lectin: Structure, Oligomerization, and Flexibility Studied by Atomic Force Microscopy

• Published in: Journal of molecular biology 2009-08, Vol.391 (1), p.246-259
• Main Authors: Jensenius, Henriette, Klein, Dionne C.G., van Hecke, Martin, Oosterkamp, Tjerk H., Schmidt, Thomas, Jensenius, Jens C.
• Format: Article
• Language: English
• Subjects: atomic force microscopy; complement; innate immunity; mannan-binding lectin; Mannose-Binding Lectin - chemistry; Mannose-Binding Lectin - metabolism; Microscopy, Atomic Force; Models, Molecular; Protein Multimerization; protein structure; Protein Structure, Quaternary; Protein Structure, Tertiary
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2009.05.083

Mannan-binding lectin (MBL) is the archetypical pathogen recognition molecule of the innate immune defense. Upon binding to microorganisms, reactions leading to the destruction of the offender ensue. MBL is an oligomer of structural subunits each composed of three identical polypeptides. We used atomic force microscopy to reveal tertiary and quaternary structures of MBL. The images in both air and buffer show a quaternary structure best described as “sertiform”, that is, a hub from which the subunits fan out. The dimensions conform to those calculated from primary and secondary structures. The subunits associate with a preferred angle of 40° between them. This angle is stable with respect to the degree of oligomerization for MBL of four subunits or more. Due to an interruption in the collagenous sequence, the arms of the subunits are expected to form a kink. We find that ∼ 30% of the subunits are kinked and the kink angle distributed, quite broadly, around 145°. The conformation and flexibility of the MBL molecule that we observe differ distinctly from the popular view of a “bouquet-like” configuration as that found for related members of the complement system such as C1q. This structural information will further the understanding of the specific functioning of the MBL pathway of complement activation.