Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition, and phagocytosis

Damaged or old erythrocytes are cleared rapidly from circulation. Because several common biochemical lesions can induce the clustering of integral membrane proteins, we have proposed that formation of microscopic protein aggregates in the membrane might constitute a cell surface marker that promotes removal of the defective/senescent cells. We demonstrate here that treatments that cluster integral membrane proteins in erythrocytes (1 mM ZnCl2, 1 mM acridine orange, and 0.35 microM melittin) induce autologous IgG binding, complement fixation, and phagocytosis by human monocytes in vitro. Removal of the clustering agents prior to incubation in autologous serum or cross-linking of cell surface proteins before addition of clustering agents prohibited the above response, while cross-linking after treatment with the clustering agents preserved the response even if the clustering agents were later removed. Furthermore, subsequent reversal of the chemical cross-link maintaining the clustered distribution also reversed the induction of IgG binding, complement deposition, and phagocytosis. Finally, by deleting or inactivating different steps in the phagocytosis pathway, the chronology of steps was shown to be: (i) integral protein clustering, (ii) IgG binding, (iii) complement deposition, and (iv) phagocytosis

Sequential phosphorylation of adjacent serine residues on the N-terminal region of cardiac troponin-I: structure-activity implications of ordered phosphorylation

AbstractWe have used NMR spectroscopy to monitor the phosphorylation of a peptide corresponding to the N-terminal region of human cardiac troponin-I (residues 17–30), encompassing the two adjacent serine residues of the dual phosphorylation site. An ordered incorporation of phosphate catalysed by PKA was observed, with phosphorylation of Ser-24 preceding that of Ser-23. Diphosphorylation induced a conformational transition in this region, involving the specific association of the Arg-22 and Ser-24P side-chains, and maximally stabilised when both phosphoserines were in the di-anionic form. The results suggest that the second phosphorylation at Ser-23 of cardiac troponin-I is of particular significance in the mechanism by which adrenaline regulates the calcium sensitivity of the myofibrillar actomyosin Mg-ATPase

Unexpected phase transition sequence in the ferroelectric Bi4Ti3O12

Authors thank Dr George Carins for experimental assistance. Y.-Y.G thanks the China Scholarships Council and the University of St Andrews for a studentship.The high-temperature phase behaviour of the ferroelectric layered perovskite Bi4Ti3O12 has been re-examined by high-resolution powder neutron diffraction. Previous studies, both experimental and theoretical, had suggested conflicting structural models and phase transition sequences, exacerbated by the complex interplay of several competing structural instabilities. Here, we confirm that Bi4Ti3O12 undergoes two separate structural transitions from the aristotype tetragonal phase (space group I4/mmm) to the ambient temperature ferroelectric phase (confirmed as monoclinic, B1a1). An unusual, and previously unconsidered, intermediate paraelectric phase is suggested to exist above TC, with tetragonal symmetry, space group P4/mbm. This phase is peculiar in displaying a unique type of octahedral tilting, in which the triple perovskite blocks of the layered structure alternate between tilted and untilted. This is rationalised in terms of the bonding requirements of the Bi3+ cations within the perovskite blocks.Publisher PDFPeer reviewe

Emergence of the Spin Polarized Domains in the Kagome Lattice Heisenberg Antiferromagnet Zn-barlowite (Zn0.95_{0.95}Cu0.05_{0.05})Cu3_{3}(OD)6_{6}FBr

Kagome lattice Heisenberg antiferromagnets are known to be highly sensitive to perturbations caused by structural disorder. NMR is a local probe ideally suited for investigating such disorder-induced effects, but in practice large distributions in the conventional one-dimensional NMR data make it difficult to distinguish the intrinsic behavior expected for pristine kagome quantum spin liquids from extrinsic effects induced by disorder. Here we report a novel two-dimensional NMR data acquisition scheme applied to Zn-barlowite (Zn$_{0.95}$Cu$_{0.05}$)Cu$_{3}$(OD)$_{6}$FBr kagome lattice, and successfully correlate the distribution of the low energy spin excitations with that of the local spin susceptibility. We present evidence for the gradual growth of domains with a local spin polarization induced by 5\% Cu$^{2+}$ defect spins occupying the interlayer non-magnetic Zn$^{2+}$ sites. These spin polarized domains account for $\sim60$\% of the sample volume at 2~K, where extrinsic gapless excitations dominate the low energy sector of spin excitations within the kagome planes.Comment: 10 figure