Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil

Area of Science:

• Biochemistry
• Structural Biology
• Immunology

Background:

• Human mannose-binding protein (MBP) is a crucial component of the innate immune system.
• MBP functions as a hexamer of trimers, with each subunit containing distinct functional domains.
• The carbohydrate recognition domain (CRD) of MBP requires calcium for effective ligand binding.

Purpose of the Study:

• To elucidate the structural basis of mannose-binding protein's recognition capabilities.
• To investigate the trimerization mechanism of MBP's neck and CRD regions.
• To understand how MBP trimers form the fundamental unit for microbial carbohydrate recognition.

Main Methods:

• A 148-residue peptide encompassing the neck and CRD of human MBP was synthesized.
• The structure of this trimeric peptide was determined using X-ray crystallography in two different crystal forms.
• Analysis of the crystal structures revealed the detailed arrangement of the neck and CRD domains.

Main Results:

• The neck region forms a stable triple alpha-helical coiled-coil structure.
• Each alpha-helix within the neck interacts intimately with a neighboring CRD.
• The spatial organization of the CRDs within the trimer was visualized, highlighting their arrangement for ligand binding.

Conclusions:

• The trimeric structure formed by the neck and CRD peptides provides a fundamental recognition unit for MBP.
• The triple alpha-helical coiled-coil of the neck domain is essential for stabilizing the trimeric conformation.
• The arrangement of CRDs suggests a mechanism for MBP's interaction with branched oligosaccharides on microbial surfaces.