C-Type Lectins (L7) Flashcards
What are some of the general functions of C-Type lectins?
Defence against invading pathogens and cell-to-cell adhesion
What is the subgroup of C-Type lectins and what is their function?
Collectins which target the carbohydrate structures on invading pathogens resulting in the agglutination and clearance of the microorganism
What is the basic unit of collectins?
A trimer consisting of: a short N-terminal region Collagen-like triple helix Alpha-helical coiled-coil neck region Three globular C-terminal CRDs
Active molecule is composed of multiple trimeric building blocks
What are mannose binding proteins?
Calcium-dependent animal lectins found in the serum and liver
What are the binding patterns for MBPs?
Weak intrinsic affinity for monovalent sugar ligand but bind avidly to multivalent ligands
How are MBP’s involved in innate immunity?
Activating complement via recognition of cell surface carbohydrates
How do MBP’s recognise carbohydrates?
Via cell surface oligosaccharide structures- calcium dependent
Occurs at the carbohydrate recognition domain (CRD) of the collectins
What is the function of hSP-D?
Modulates allergic reactions by binding glycosylated allergens
Massice cross-linking of pathogens via multiple CRDs
Present bound pathogen directly to immune cells
What is the structure of hsP-D
X-shaped structure of 4 trimers, over 100nm long
What is the biomedical significance of hSP-D?
Correlation between hSP-D polymorphism and susceptibility to pneumonia
Correlation between hSP-D levels and susceptibility to severe lung infection, allergy and asthma
Deficiency of hSP-D in patients with cystic fibrosis
What is the structure of the hSP-D active fragment?
An alpha-helical coiled neck region and globular carbohydrate binding domains (CRDs)
How is the calcium ion ligated in the CRD within the hSP-D?
Ligated by Glu321, Asn323, Glu329, Asn341, Asp342 and the carbonyl group of 342 and also by 2 waters
What is the structure of maltose bound hSP-D?
Very small conformational change in the binding pocket occurring when the site is occupied with ligand.
Hydrogen bonding interactions between the sugar ring hydroxyls and the bound Ca ion
O3’ interacts with Glu321 and Asn323
O4’ interacts with Glu329 and Asn341
Glc3 is aligned over but slightly offset with the ring of Phe335 and the plane of the Glc3 ring is deflected ~90 degrees relative to Glc1
Glc3 interacts with Thr336 and with Asn337
Glc2 is deflected towards Phe335 and there is an associated totling of Glc1
How does hSP-D distinguish between self and non-self?
Spatial arrangement of individual binding sites does not allow multivalent binding to a typical mammalian high-mannose oligosaccharide but favours high avidity binding to the widely spaced repetitive sugar arrays on pathogen surfaces.
Relies on the pattern of the binding sites
