Structure of a novel ribosome-inactivating protein from a hemi-parasitic plant inhabiting the northwestern Himalayas.
This is the first report of the structural studies of a novel ribosome-inactivating protein (RIP) obtained from the Himalayan mistletoe (Viscum album) (HmRip). HmRip is a type II heterodimeric protein consisting of a toxic enzyme (A-chain) with an active site for ribosome inactivation and a lectin subunit (B-chain) with well defined sugar-binding sites. The crystal structure of HmRip has been determined at 3.8 A resolution and refined to a crystallographic R factor of 0.228 (R(free) = 0.271). A comparison of this structure with other type II RIPs reveals the presence of distinct structural features in the active site of the A-chain and in the 2gamma sugar-binding site of the B-chain. The conformation of the side chain of Tyr110, which is a conserved active-site residue in the A subunit, is strikingly different from those observed in other mistletoe RIPs, indicating its unique substrate-binding preference. The deletion of two important residues from the kink region after Ala231 in the 2gamma subdomain of the B-chain results in a significantly different conformation of the sugar-binding pocket. A ribosome-recognition site has also been identified in HmRip. The site is a shallow cavity, with the conserved residues Arg51, Asp70, Thr72 and Asn73 involved in the binding. The conformations of the antigenic epitopes of residues 1-20, 85-103 and 206-223 differ from those observed in other type II RIPs, resulting in the distinct antigenicity and pharmacological properties of HmRip.
Mishra
Vandana
V
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
Ethayathulla
Abdul S
AS
Sharma
Radhey S
RS
Yadav
Savita
S
Krauspenhaar
Ruth
R
Betzel
Christian
C
Babu
Cherukuri R
CR
Singh
Tej P
TP
D000595:Amino Acid Sequence; D000941:Antigens; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004583:Electrons; D000939:Epitopes / Q000737:chemistry; D006031:Glycosylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D028321:Plant Preparations / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D054790:Ribosome Inactivating Proteins, Type 2; D012270:Ribosomes / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014118:Toxins, Biological / Q000737:chemistry*; D028182:Viscum album / Q000378:metabolism
D000941:Antigens; D002241:Carbohydrates; D018076:DNA, Complementary; D000939:Epitopes; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum