LYMPHOCYTE ACTIVATION RECEPTORS: NEW STRUCTURAL PARADIGMS IN THE GROUP V OF C-TYPE ANIMAL LECTINS
Pavlíček J.1, Ettrich R.2, Kopecký V. Jr.3, Man P.4, Vrbacký M.5, Bezouška K.1,2
1 Department of Biochemistry, Faculty of
Science, Charles University Prague, Hlavova 8, 12840 Praha.
2 Laboratory of
High Performance Computing, Institute of Physical Biology USB and Institute of
Landscape Ecology AS CR, Zámek 136, CZ-37333 Nové Hrady.
3 Institute of Physics, Charles University
in Prague, Ke Karlovu 5, CZ-12116 Praha.
4 Institute of Microbiology, Academy of
Sciences of the Czech Republic, CZ-14220 Praha.
5 Department of Pathological Physiology, 1st
Medical Faculty, Charles University in Prague, U nemocnice 5, CZ-12853 Praha.
From the point of view of structural biology, our understanding of the structure – function relationships in the C-type lectin family remains fragmentary. By far the best characterized molecule of the whole family is the soluble mannose binding protein studied protein crystallography. This protein binds to calcium ions in the ligand-binding domain, and the binding of calcium is intimately linked to the recognition of carbohydrates. Some of the receptors of natural killer lymphocytes have been also structurally characterized. Since this group is evolutionarily most divergent, interesting structural paradigms have been observed with regard to binding of calcium, carbohydrates, and other ligands. In NKR-P1, calcxium may not be easily removed by chelating agents because of its unique chemical nature. In CD69, binding of calcium causes a structural shift in amino acids important for binding of carbohydrates. Structural studies have also allowed us to understand an interesting preference of these receptors for either linear (NKR-P1) or branched (CD69) carbohydrate sequences.sugars. Remodeling of the binding surface in CD94 or Ly-49 opens the way for specific recognition of protein and peptide ligands.
This work was supported by Ministry of
Education of the Czech Republic No. MSM 0021620808, by Institutional Research Concept
No. AVOZ 50200510, by Grant Agency of the Czech Republic No. 301/05/P567, and by
Grant Agency of the Academy
of Sciences of the Czech Republic No. A5020403.