The x-ray structures of a murine MHC class I molecule (H-2K b ) were determined in complex with two different viral peptides, derived from the vesicular stomatitis virus nucleoprotein (52-59), VSV-8, and Sendai (324-332), SEV-9. H-2K complexes refined at 2.3 Å for VSV-8 2.5 structure exhibits high degree similarity human HLA I, although individual domains can have slightly altered dispositions. Both peptides bind extended conformations most their surfaces buried binding groove. nonamer...

CD1 represents a third lineage of antigen-presenting molecules that are distantly related to major histocompatibility complex (MHC) in the immune system. The crystal structure mouse CD1d1, corresponding human CD1d, at 2.8 Å resolution shows adopts an MHC fold is more closely class I than II. binding groove, although significantly narrower, substantially larger because increased depth and it has only two pockets almost completely hydrophobic. extreme hydrophobicity shape site consistent with...

Erythropoietin receptor (EPOR) is thought to be activated by ligand-induced homodimerization. However, structures of agonist and antagonist peptide complexes EPOR, as well an EPO-EPOR complex, have shown that the actual dimer configuration critical for biological response signal efficiency. The crystal structure extracellular domain EPOR in its unliganded form at 2.4 angstrom resolution has revealed a which individual membrane-spanning intracellular domains would too far apart permit...

The functional mimicry of a protein by an unrelated small molecule has been formidable challenge. Now, however, the biological activity 166-residue hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine receptor mimicked 20-residue cyclic peptide in sequence to natural ligand. crystal structure at 2.8 Å resolution complex this agonist extracellular domain EPO reveals that dimer induces almost perfect twofold dimerization receptor. assembly differs from human hormone...

Staphylococcus aureus produces a virulence factor, protein A (SpA), that contains five homologous Ig-binding domains. The interactions of SpA with the Fab region membrane-anchored Igs can stimulate large fraction B cells, contributing to lymphocyte clonal selection. To understand molecular basis for this activity, we have solved crystal structure complex between domain D and fragment human IgM antibody 2.7-Å resolution. In complex, helices II III interact variable heavy chain (V H ) through...

Structural and mechanistic studies show that when the selection criteria of immune system are changed, catalytic antibodies have efficiency natural enzymes evolve, but much more accepting a wide range substrates. The were prepared by reactive immunization, process whereby changed from simple binding to chemical reactivity. This yielded aldolase approximated rate acceleration enzyme used in glycolysis. Unlike enzyme, however, antibody aldolases catalyzed variety aldol reactions...

Human placental alkaline phosphatase (PLAP) is one of three tissue-specific human APs extensively studied because its ectopic expression in tumors. The crystal structure, determined at 1.8-Å resolution, reveals that during evolution, only the overall features enzyme have been conserved with respect toEscherichia coli. surface deeply mutated 8% residues common, and active site, strictly necessary to perform catalysis preserved. Additional structural elements aid an understanding allosteric...

Sequence analysis of peptides naturally presented by major histocompatibility complex (MHC) class I molecules has revealed allele-specific motifs in which the peptide length and residues observed at certain positions are restricted. Nevertheless, containing standard motif often fail to bind with high affinity or form physiologically stable complexes. Here we present crystal structure a well-characterized antigenic from ovalbumin [OVA-8, ovalbumin-(257-264), SIINFEKL] murine MHC H-2Kb...

The crystal structure of a complex between 24-amino acid peptide from the third variable (V3) loop human immunodeficiency virus-type 1 (HIV-1) gp120 and Fab fragment broadly neutralizing antibody (59.1) was determined to 3 angstrom resolution. tip V3 containing Gly-Pro-Gly-Arg-Ala-Phe sequence adopts double-turn conformation, which may be basis its conservation in many HIV-1 isolates. A complete map principal determinant constructed by stitching together structures peptides bound 59.1 an...

The human tissue nonspecific alkaline phosphatase (TNAP) is found in liver, kidney, and bone. Mutations the TNAP gene can lead to Hypophosphatasia, a rare inborn disease that characterized by defective bone mineralization. 74% homologous placental (PLAP) whose crystal structure has been recently determined at atomic resolution (Le Du, M. H., Stigbrand, T., Taussig, J., Ménez, A., Stura, E. A. (2001) <i>J. Biol. Chem</i>, 276, 9158–9165). degree of homology allowed us build reliable model...

Boiga dendrophila (mangrove catsnake) is a colubrid snake that lives in Southeast Asian lowland rainforests and mangrove swamps preys primarily on birds. We have isolated, purified, sequenced novel toxin from its venom, which we named denmotoxin. It monomeric polypeptide of 77 amino acid residues with five disulfide bridges. In organ bath experiments, it displayed potent postsynaptic neuromuscular activity irreversibly inhibited indirectly stimulated twitches chick biventer cervicis...

The crystal structure of the Fab fragment a human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibody has been determined at 2.8 A resolution in complex with linear 16-residue peptide from third hypervariable region (V3) gp120. first 9 residues are ordered electron density maps, and their conformation is partial agreement beta-strand-type II beta-turn predicted for this portion V3 loop. Notably, several that well conserved among different HIV-1 isolates contact nonpolar...

The three-dimensional structure of a catalytic antibody (1F7) with chorismate mutase activity has been determined to 3.0 A resolution as complex transition state analog. structural data suggest that the stabilizes same conformationally restricted pericyclic occurs in uncatalyzed reaction. Overall shape and charge complementarity between combining site analog dictate preferential binding correct substrate enantiomer conformation appropriate for Comparison enzyme indicates an overall...

A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a protein fold, typical for "nonconventional" toxins such as denmotoxin, bucandin, candoxin. This is first colubrid toxin dimer, covalently connected via an interchain disulfide bond. showed taxon-specific...

Cellular immunity is mediated by the interaction of an αβ T cell receptor (TCR) with a peptide presented within context major histocompatibility complex (MHC) molecule. Alloreactive cells have TCRs that can recognize both self- and foreign peptide–MHC (pMHC) complexes, implying TCR has significant complementarity different pMHC. To characterize molecular basis for alloreactive recognition pMHC, we produced soluble, recombinant form in Drosophila melanogaster cells. This TCR, 2C, expressed as...

A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of immune system. The catalytic 13G5 catalyzes a disfavored exo transformation in reaction for which there is no natural enzyme counterpart and that yields single regioisomer high enantiomeric excess. crystal structure Fab complex with ferrocenyl inhibitor containing essential haptenic core elicited determined at 1.95 angstrom resolution. Three key residues appear to be responsible observed...