Multivalency in Lectins

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Presentation transcript:

Multivalency in Lectins M. Vijayan Molecular Biophysics Unit Indian 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 Peanut lectin (PNA) Tetramer, Mr 1,10,000; Non-glycosylated; galactose specific; specific to T-antigen (Gal1-3GalNAc) at disaccharide level Basic winged bean lectin (WBA I) Dimer, Mr 58,000; glycosylated; Gal/GalNAc specific; 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/GalNAc specific; specific to blood group O and binds weakly to A and B

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

Jackfruit

Jacalin: A lectin from jackfruit seeds Nat. Struct. Biol. (1996) 3, 596-603 J. Mol. Biol. (2002) 321, 637-645 J. Mol. Biol. (2003) 332, 217-228 Tetramer, Mr 66,000; glycosylated; Gal/GalNAc specific; Specific to T-antigen at disaccharide level New lectin fold characteristic of the moraceae family

Hydrogen-bonding interactions between jacalin and galactose Post translational proteolysis is used as a strategy for generating ligand specificity

Composite view of binding region Secondary site A Secondary site B Primary site

Structure and interactions of artocarpin J. Mol. Biol (2002) 317, 237-247 J. Mol. Biol (2004) 338,757-770 Tetrameric, Mr 65,000; Non-glycosylated; Mannose-specific

Snake gourd

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

Snake gourd lectin has no ribosome inactivating property Red SGSL Blue Trichosanthin

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-PLOR DENZO 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 interactions G. Ramachandraiah, Nagasuma R. Chandra, A. Surolia and M. Vijayan (2003) Glycobiology 13, 765-775 2 4 6 8.6 11.6 NI 7.3 Man1-2Man Man1-3Man Man1-4Man Man1-6Man 28.8 29.0 Man5 Man3

Man7Gn2Asn 6545 7200 Man8Gn2Asn 14120 Man9Gn2Asn M5 M6 M7 N8 N9 N8 M5

Single cross-linking 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

Double cross-linking Term. pairs: 12C2 Site pairs: 6P2 Total: 12C2 × 6P2 :1980 |Tij-Sij| <=3.0 Å Accepted pairs of dimers: Short contacts <=40

No. of Single links Double links Tri Penta Hepta Octa Nona 24 70 61 94 3 7 36 20 64

M1F-M3E