RESUMO
Greece and Romania reported an increased number of HIV cases among injecting drug users (IDUs) during 2011. Most European countries reported no changes in the rate of newly diagnosed cases of HIV or HIV prevalence in IDUs; however, six countries did report increases and several additional countries reported increases in injecting risk indicators or low coverage of prevention services. These indicate a potential risk for increased HIV transmission and future outbreaks unless adequate prevention is implemented.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV/patogenicidade , Abuso de Substâncias por Via Intravenosa , Feminino , Grécia/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Hepacivirus/patogenicidade , Hepatite C/epidemiologia , Hepatite C/transmissão , Hepatite C/virologia , Humanos , Cobertura do Seguro , Masculino , Uso Comum de Agulhas e Seringas , Prevalência , Medição de Risco , Fatores de Risco , Romênia/epidemiologiaRESUMO
A high resolution structure of alpha-conotoxin EI has been determined by (1)H NMR spectroscopy and molecular modeling. alpha-Conotoxin EI has the same disulfide framework as alpha 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the alpha 3/5 and alpha A conotoxins. The unique binding preference of alpha-conotoxin EI to the alpha(1)/delta subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various alpha-conotoxins possessing distinct receptor subtype specificities. Structural comparison of alpha-conotoxin EI with the gamma-subunit favoring alpha-conotoxin GI suggests that the Torpedo delta-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven alpha-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is approximately 20 A (height) x 20 A (width) x 15 A (thickness).
Assuntos
Conotoxinas/química , Estrutura Terciária de Proteína , Receptores Nicotínicos/química , Sequência de Aminoácidos , Animais , Conotoxinas/metabolismo , Dissulfetos/química , Modelos Moleculares , Dados de Sequência Molecular , Junção Neuromuscular/química , Antagonistas Nicotínicos/química , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Receptores Nicotínicos/metabolismo , Torpedo/metabolismoRESUMO
DNA transcription is initiated by a small regulatory region of transactivators known as the transactivation domain. In contrast to the rapid progress made on the functional aspect of this promiscuous domain, its structural feature is still poorly characterized. Here, our multidimensional NMR study reveals that an unbound full-length p53 transactivation domain, although similar to the recently discovered group of loosely folded proteins in that it does not have tertiary structure, is nevertheless populated by an amphipathic helix and two nascent turns. The helix is formed by residues Thr(18)-Leu(26) (Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu), whereas the two turns are formed by residues Met(40)-Met(44) and Asp(48)-Trp(53), respectively. It is remarkable that these local secondary structures are selectively formed by functionally critical and positionally conserved hydrophobic residues present in several acidic transactivation domains. This observation suggests that such local structures are general features of acidic transactivation domains and may represent "specificity determinants" (Ptashne, M., and Gann, A. A. F. (1997), Nature 386, 569-577) that are important for transcriptional activity.
