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Multivalency in Lectins

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Presentation on theme: "Multivalency in Lectins"— Presentation transcript:

1 Multivalency in Lectins
M. Vijayan Molecular Biophysics Unit Indian Institute of Science Bangalore

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3 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

4 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

5 Legume lectins: peanut lectin, winged bean basic and
acidic lectins and their complexes PNAS (1994) 91, JMB (1996) 259, JBC (1996) 271, Curr. Sci. (1997) 72, JMB (1998) 276, Glycobiology (1998) 10, JACS (1998) 120, Proteins SFG (1999) 35, 58-69 Acta Cryst. (1999) D55, JMB (2000) 302, Proteins SFG (2001) 43, JBC (2001) 276, Protein Eng. (2001) 14, Acta Cryst. (2001) D57, Acta Cryst. (2003) D59,

6 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

7 Jackfruit

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

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

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

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

12 Snake gourd

13 Structure of snake gourd lectin
Acta Cryst. (2001) D57, Heterodimeric, Mr 62,000; Glycosylated; Galactose specific Amino acid sequence not available Structure similar to that of typeII RIP’s

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

15 Structure and interactions of garlic lectin
JMB (1999) 285, Dimeric, Mr 24,000; Non-glycosylated; Mannose specific

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17 Garlic lectin: Re-refinement using reprocessed data
G. Ramachandraiah, Nagasuma R. Chandra, A. Surolia and M. Vijayan (2002) Acta Cryst. D58, 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

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19 Garlic lectin-olygosaccharide interactions
G. Ramachandraiah, Nagasuma R. Chandra, A. Surolia and M. Vijayan (2003) Glycobiology 13, 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

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

21 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

22 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

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

24 M1F-M3E

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