Naturally processed peptides from two disease-resistance-associated HLA-DR13 alleles show related sequence motifs and the effects of the dimorphism at position 86 of the HLA-DR beta chain.

HLA-DR13 has been associated with resistance to two major infectious diseases of humans. To investigate the peptide binding specificity of two HLA-DR13 molecules and the effects of the Gly/Val dimorphism at position 86 of the HLA-DR beta chain on natural peptide ligands, these peptides were acid-eluted from immunoaffinity-purified HLA-DRB1*1301 and -DRB1*1302, molecules that differ only at this position. The eluted peptides were subjected to pool sequencing or individual peptide sequencing by tandem MS or Edman microsequencing. Sequences were obtained for 23 peptides from nine source proteins. Three pool sequences for each allele and the sequences of individual peptides were used to define binding motifs for each allele. Binding specificities varied only at the primary hydrophobic anchor residue, the differences being a preference for the aromatic amino acids Tyr and Phe in DRB1*1302 and a preference for Val in DRB1*1301. Synthetic analogues of the eluted peptides showed allele specificity in their binding to purified HLA-DR, and Ala-substituted peptides were used to identify the primary anchor residues for binding. The failure of some peptides eluted from DRB1*1302 (those that use aromatic amino acids as primary anchors) to bind to DRB1*1301 confirmed the different preferences for peptide anchor residues conferred by the Gly-->Val change at position 86. These data suggest a molecular basis for the differential associations of HLA-DRB1*1301 and DRB1*1302 with resistance to severe malaria and clearance of hepatitis B virus infection.

Library of libraries: approach to synthetic combinatorial library design and screening of "pharmacophore" motifs.

Construction of synthetic combinatorial libraries is described that allows for the generation of a library of motifs rather than a library of compounds. Peptide libraries based on this strategy were synthesized and screened with model targets streptavidin and anti-beta-endorphin antibody. The screens resulted in observation of expected motifs providing evidence of the effectiveness of the suggested approach.

Regulation of cell signaling by the cytoplasmic domains of the heat-stable enterotoxin receptor: identification of autoinhibitory and activating motifs.

Infection with enterotoxigenic Escherichia coli is a leading cause of traveler's diarrhea. Many enterotoxigenic E. coli strains produce heat-stable enterotoxin (ST), a peptide that binds to the intestinal receptor guanylyl cyclase C known as STaR. The toxin-receptor interaction elevates intracellular cGMP, which then activates apical chloride secretion, resulting in secretory diarrhea. In this report, we examine how the intracellular domains of STaR participate in the propagation and regulation of signaling. We show that STaR exists as an oligomer in both the presence and the absence of toxin. We also demonstrate that deletion of the intracellular kinase-homology domain produces a constitutively active mutant, suggesting that this domain subserves an autoinhibitory function. Finally, we constructed a point mutant within a highly conserved region of the cyclase domain that completely inactivates the catalytic activity of guanylyl cyclase. Cotransfection of this point mutant with wild-type receptor causes a dominant-negative effect on receptor activation. This suggests that interaction of receptor subunits is required for toxin-induced activation and that the cyclase domain is involved in this essential interaction. We propose that the binding of ST to STaR promotes a conformational change across the cell membrane. This removes the inhibitory effects of the kinase-homology domain and promotes an interaction between cyclase domains that leads to receptor activation. The data suggest a paradigm of signal transduction that may also be relevant to other members of the guanylyl cyclase receptor family.

Satanella-quadrille : sur des motifs du ballet Satanella de Pugni /

For piano.

Bowl with Fish Motifs

Pottery, Islamic, Ilkhanid; 5 in.x 11 17/64 in.; stonepaste; molded and glazed

Mexican motifs.

Mode of access: Internet.

Motifs pour engager les Ecclesiastiques a travailler au salut des Ames : tirez de la sainte ecriture, des conciles, & des péres ... /

Mode of access: Internet.

Code de Commerce expliqué par ses motifs et par des exemples : avec la solution, sous chaque article, des difficultés ainsi que des principales questions que présente le texte, et la définition de tous les termes de droit, suivi d'un formulaire... /

Mode of access: Internet.

Loi de la procédure civile du canton de Genève, suivie de l'exposé des motifs /

Mode of access: Internet.

Réflexions d'un suisse, sur les motifs de la guerre présente.

Mode of access: Internet.

Motifs et discours prononcés lors de la publication du Code Civil /

Port. con grab. xil.

Code civil expliqué par ses motifs, par des examples, et par la jurisprudence : avec la solution, sous chaque article, des difficultés... ; suivi d'un formulaire /

Mode of access: Internet.

Code de Commerce expliqué par ses motifs, par des exemples, et par la jurisprudence, avec la solution, sous chaque article, des difficultés, ainsi que des principales questions que présente le texte, la définition des termes de droit, et la reproduction des motifs de tous les arrèts-principes, suivi d'un formulaire /

Mode of access: Internet.

Motifs pour engager les Ecclesiastiques a travailler au salut des Ames : tirez de la sainte ecriture, des conciles, & des péres ... /

Mode of access: Internet.

Le Livre rouge, ou Liste des pensions secrettes, sur le trésor public; contenant les noms & qualités des pensionnaires, l'état de leurs services, & des observations sur les motifs qui leur ont mérité leur traitement.

Printed in red.