HIV hides its genome inside a proteinaceous shell formed by capsid hexamers to evade detection and degradation in the cytosol of host cells; however, the capsid also hinders access of substrates that are essential for reverse transcription, such as deoxynucleoside triphosphates (dNTPs). Thus far, it was unclear how HIV imported dNTPs into the capsid. Jacques et al. now show that a dynamic pore exists in the centre of each capsid hexamer that enables the entry of dNTPs and thereby supports reverse transcription inside the capsid.
The HIV capsid is a conical structure that is formed by a single protein, the capsid protein. Capsid monomers are arranged into a symmetrical hexamer around a central axis and the authors hypothesized that a pore might exist along this axis. However, there was no evidence for such a pore from previous hexamer structures. In fact, previous structures showed that the amino-terminal β-hairpins of each capsid monomer blocked the opening of such a potential pore. When the authors examined this region more closely, including in structures of capsid monomers, they noticed that the β-hairpin is flexible and can assume different conformations by tilting up to 15 Å away from the axis of symmetry. Indeed, when reconstructing a capsid hexamer based on monomer structures with this 'open' β-hairpin conformation, a central pore is formed. The conformational change is likely to depend on the protonation status of a histidine residue at the base of the β-hairpin. This is supported by the observation that structures that were obtained at a high crystallisation pH adopted a closed conformation, whereas structures that were obtained at a low pH adopted an open conformation. Interestingly, at physiological pH, the β-hairpin assumes an intermediate position, indicating high flexibility. Thus, the β-hairpin functions as a 'molecular iris' that controls entry to a central pore in the capsid.
A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found existing drug compounds that can both stop Zika from replicating in the body and from damaging the crucial fetal brain cells that lead to birth defects in newborns. One of the drugs is already on the …
Protein fragment could provide a defense when antibiotics fail | Researchers at Harvard-affiliated Boston Children’s Hospital are looking at new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.
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Researchers at the Stanford University School of Medicine have made an important breakthrough in their ongoing efforts to develop a diagnostic test that can tell health-care providers whether a patient has a bacterial infectio
Randy R. Brutkiewicz + Author Affiliations Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 Address correspondence and reprint requests to Dr. Randy R. Brutkiewicz, Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Building R2, Room 302, Indianapolis, IN 46202-5181. E-mail address: firstname.lastname@example.org Abstract Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation, a necessary first step in the activation of innate and adaptive T cells. In this brief review, I discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s), if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity, and cancer.
UT Southwestern researchers (l-r) Dr. Erdal Toprak, Dr. Seth Daly, Yusuf Talha Tamer, and Dr. David Greenberg reported successful use of a synthetic molecule to enhance antibiotic effectiveness agains..
Cellular and Molecular Immunology aims to report the dynamic progress being made in China and abroad in immunological research, and welcomes high-quality Research Articles, Reviews and Brief Reports across a broad range of topics including, but not...
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A study led by researchers at The Saban Research Institute of Children's Hospital Los Angeles (CHLA) suggests that maternal HIV infection influences the microbiome of their HIV-uninfected infants. Their findings, reporte
The complement system, crosstalk connections, the involvement of complement in clinical conditions and promising therapeutic approaches. Review by Ricklin, Reis and Lambris, free to access for a limited time.
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