RESUMEN
Bordetella pertussis establishes infection by attaching to epithelial cells of the respiratory tract. One of its adhesins is filamentous haemagglutinin (FHA), a 500-A-long secreted protein that is rich in beta-structure and contains two regions, R1 and R2, of tandem 19-residue repeats. Two models have been proposed in which the central shaft is (i) a hairpin made up of a pairing of two long antiparallel beta-sheets; or (ii) a beta-helix in which the polypeptide chain is coiled to form three long parallel beta-sheets. We have analysed a truncated variant of FHA by electron microscopy (negative staining, shadowing and scanning transmission electron microscopy of unstained specimens): these observations support the latter model. Further support comes from detailed sequence analysis and molecular modelling studies. We applied a profile search method to the sequences adjacent to and between R1 and R2 and found additional "covert" copies of the same motifs that may be recognized in overt form in the R1 and R2 sequence repeats. Their total number is sufficient to support the tenet of the beta-helix model that the shaft domain--a 350 A rod--should consist of a continuous run of these motifs, apart from loop inserts. The N-terminus, which does not contain such repeats, was found to be weakly homologous to cyclodextrin transferase, a protein of known immunoglobulin-like structure. Drawing on crystal structures of known beta-helical proteins, we developed structural models of the coil motifs putatively formed by the R1 and R2 repeats. Finally, we applied the same profile search method to the sequence database and found several other proteins--all large secreted proteins of bacterial provenance--that have similar repeats and probably also similar structures.
Asunto(s)
Adhesinas Bacterianas/química , Bordetella pertussis/química , Hemaglutininas/química , Factores de Virulencia de Bordetella , Adhesinas Bacterianas/metabolismo , Adhesinas Bacterianas/ultraestructura , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Antígenos Bacterianos/química , Antígenos Bacterianos/ultraestructura , Vacunas Bacterianas , Hemaglutininas/metabolismo , Hemaglutininas/ultraestructura , Microscopía Electrónica de Transmisión de Rastreo , Modelos Moleculares , Datos de Secuencia Molecular , Peso Molecular , Coloración Negativa , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Secuencias Repetitivas de Aminoácido , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Técnica Histológica de SombreadoRESUMEN
Four hundred and eighty-four adolescents and young adults at an inpatient psychiatric facility were diagnosed as nonverbal learning disabled, verbal learning disabled, general learning disabled, or normal psychiatric controls. The nonverbal learning disabled group had the highest incidence of depression and was clearly different from the reading disabled group (66.3% vs. 33.3%). Nondisabled subjects were significantly more likely than the other subjects to be diagnosed with adjustment problems. Depressed subjects were significantly younger and more likely to be female. This study supports the contention that right-hemisphere, white-matter, arithmetic-disabled adolescents and young adults in a psychiatric population are at greater risk for depression than are psychiatric patients not showing this pattern.
