Multivalency in Lectins M. Vijayan Molecular Biophysics Unit Indian Institute of Science Bangalore...
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Transcript of Multivalency in Lectins M. Vijayan Molecular Biophysics Unit Indian Institute of Science Bangalore...
Multivalency in Lectins
M. Vijayan
Molecular Biophysics UnitIndian Institute of Science
Bangalore 560012
Plant Lectin Families
I Legume lectins Jelly roll
II Cereal lectins Hevein domain
III Moraceae lectins -prism I
IV Bulb lectins -prism II
V Ricin, Amaranthin etc -trefoil
Legume lectins: peanut lectin, winged bean basic and acidic lectins and their complexes
Basic winged bean lectin (WBA I)
Dimer, Mr 58,000; glycosylated; Gal/GalNAcspecific; specific to blood group A and less to B, does not bind O
Acidic winged bean lectin (WBA II)
Dimer, Mr 58,000; glycosylated; Gal/GalNAcspecific; specific to blood group O and binds weakly to A and B
Peanut lectin (PNA)
Tetramer, Mr 1,10,000; Non-glycosylated;galactose specific; specific to T-antigen (Gal1-3GalNAc) at disaccharide level
Legume lectins: peanut lectin, winged bean basic and acidic lectins and their complexes
• PNAS (1994) 91, 227-231• JMB (1996) 259, 281-291• JBC (1996) 271, 21209-21213• Curr. Sci. (1997) 72, 855-861• JMB (1998) 276, 787-796• Glycobiology (1998) 10, 1007-1012• JACS (1998) 120, 11297-11303• Proteins SFG (1999) 35, 58-69• Acta Cryst. (1999) D55, 1375-1382• JMB (2000) 302, 1129-1137• Proteins SFG (2001) 43, 260-270• JBC (2001) 276, 40734-40739• Protein Eng. (2001) 14, 857-866• Acta Cryst. (2001) D57, 1584-1594• Acta Cryst. (2003) D59, 2254-2256
Legume lectins: peanut lectin, winged bean basic and acidic lectins and their complexes
• Multimeric proteins can assume open quaternary structures
• High variability in quaternary structure while the tertiary structure is essentially same
• Water bridges as a strategy for generating ligand specificity
• Role of loop length and aromatic interactions in generating carbohydrate specificity
• Structure-based mutational studies
Jacalin: A lectin from jackfruit seeds
• Tetramer, Mr 66,000; glycosylated; Gal/GalNAc specific; Specific to T-antigen at disaccharide level• New lectin fold characteristic of the moraceae family
Nat. Struct. Biol. (1996) 3, 596-603 J. Mol. Biol. (2002) 321, 637-645 J. Mol. Biol. (2003) 332, 217-228
Hydrogen-bonding interactions between jacalin and galactose
• Post translational proteolysis is used as a strategy for generating ligand specificity
Structure and interactions of artocarpin
J. Mol. Biol (2002) 317, 237-247J. Mol. Biol (2004) 338,757-770
• Tetrameric, Mr 65,000;
• Non-glycosylated;
• Mannose-specific
Structure of snake gourd lectin
Acta Cryst. (2001) D57, 912-914
• Heterodimeric, Mr 62,000; Glycosylated; Galactose specific
• Amino acid sequence not available
• Structure similar to that of typeII RIP’s
Structure and interactions of garlic lectin
JMB (1999) 285, 1157-1168
• Dimeric, Mr 24,000;
• Non-glycosylated;
• Mannose specific
Garlic lectin: Re-refinement using reprocessed data
G. Ramachandraiah, Nagasuma R. Chandra, A. Surolia and M. Vijayan(2002) Acta Cryst. D58, 414-420
XDS X-PLORDENZO CNS
• Resolution increased from 2.8Å (effective) to 2.2Å • Isolectins could be identified with confidence
• Asymmetric unit contains two heterodimers. Better definition of the structure
Garlic lectin-olygosaccharide interactionsG. Ramachandraiah, Nagasuma R. Chandra, A. Surolia and M. Vijayan(2003) Glycobiology 13, 765-775
Man1-2Man
2 64
Man1-3Man Man1-4Man Man1-6Man
Man3 Man5
8.6 11.6 NI 7.3
28.829.0
• Tri : 6 × 6: 36• Penta : 12 × 6: 72• Hepta : 12 × 6: 72• Octa : 12 × 6: 72• Nona : 12 × 6: 72
Accepted pairs of dimers:Short contacts <=20
Single cross-linking
Term. pairs: 12C2
Site pairs: 6P2
Total: 12C2 × 6P2
:1980
|Tij-Sij| <=3.0 Å
Accepted pairs of dimers:Short contacts <=40
Double cross-linking