Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system.
The human glioma pathogenesis-related protein (GliPR) is highly expressed in the brain tumor glioblastoma multiforme and exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has an important role for the plant defense system. A molecular model of GliPR was computed with the distance geometry program DIANA on the basis of a P14a-GliPR sequence alignment and a set of 1,200 experimental NMR conformational constraints collected with P14a. The GliPR structure is represented by a group of 20 conformers with small residual DIANA target function values, low AMBER-energies after restrained energy-minimization with the program OPAL, and an average rms deviation relative to the mean of 1.6 A for the backbone heavy atoms. Comparison of the GliPR model with the P14a structure lead to the identification of a common partially solvent-exposed spatial cluster of four amino acid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration. This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system.
Szyperski
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T
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule-Hönggerberg, CH-8093 Zurich, Switzerland.
Fernández
C
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Mumenthaler
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Wüthrich
K
K
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D004220:Disulfides; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry*; D010944:Plants; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D004220:Disulfides; C094538:GLIPR1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C105039:PR1B1 protein, Lycopersicon esculentum; D010940:Plant Proteins