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

Abstract

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.