Abstract:
:The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an appropriate coreceptor, which triggers structural changes in Env that lead to fusion between the viral and cellular membranes. The major HIV-1 coreceptors are the seven transmembrane domain chemokine receptors CCR5 and CXCR4. The type of coreceptor used by a virus strain is an important determinant of viral tropism and pathogenesis, and virus-receptor interactions can be therapeutic targets. However, Envs from many virus strains interact with CXCR4 and CCR5 with low affinity such that direct study of this important interaction is difficult if not impossible using standard cell-surface binding techniques. We have developed an approach that makes it possible to study ligand binding to membrane proteins, including Env-coreceptor interactions, using an optical biosensor. CCR5, CXCR4, and other membrane proteins were incorporated into retrovirus particles, which were purified and attached to the biosensor surface. Binding of conformationally sensitive antibodies as well as Env to these receptors was readily detected. The equilibrium dissociation constant for the interaction between an Env derived from the prototype HIV-1 strain IIIB for CXCR4 was approximately 500 nM, explaining the difficulty in measuring this interaction using standard equilibrium binding techniques. Retroviral pseudotypes represent easily produced, stable, homogenous structures that can be used to present a wide array of single and multiple membrane-spanning proteins in a native lipid environment for biosensor studies, thus avoiding the need for detergent solubilization, purification, and reconstitution. The approach should have general applicability and can be used to correlate Env-receptor binding constants to viral tropism and pathogenesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Hoffman TL,Canziani G,Jia L,Rucker J,Doms RWdoi
10.1073/pnas.190274097keywords:
subject
Has Abstractpub_date
2000-10-10 00:00:00pages
11215-20issue
21eissn
0027-8424issn
1091-6490pii
190274097journal_volume
97pub_type
杂志文章abstract::Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.8.3339
更新日期:1991-04-15 00:00:00
abstract::The plasma iron turnover was measured in 19 normal subjects. A correlation was found between plasma iron concentration and plasma iron turnover. In addition to the turnover of 55Fe at normal plasma iron concentration (predominantly monoferric transferrin), a second turnover in which the labeled plasma was saturated wi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.3.1559
更新日期:1978-03-01 00:00:00
abstract::The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-ca...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1306437110
更新日期:2013-10-15 00:00:00
abstract::An analysis of taxonomic longevity for species of the two Cenozoic radiations of Caribbean planktonic foraminifera shows strong similarity in longevity for extinct taxa, though extant species of the latter radiation are biased towards longer-lived forms. In this case, the present is not the key to the past. A simple o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.17.5478
更新日期:1984-09-01 00:00:00
abstract::Detection and avoidance of impending obstacles is crucial to preventing head and body injuries in daily life. To safely avoid obstacles, locations of objects approaching the body surface are usually detected via the visual system and then used by the motor system to guide defensive movements. Mediating between visual ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1207946109
更新日期:2012-10-30 00:00:00
abstract::An effective plant alkaloid chemical defense requires a variety of transport processes, but few alkaloid transporters have been characterized at the molecular level. Previously, a gene fragment encoding a putative plasma membrane proton symporter was isolated, because it was coordinately regulated with several nicotin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1108620108
更新日期:2011-11-01 00:00:00
abstract::Murine fetal thymus lobes isolated from both normal and scid/scid mice can be colonized by donor cells from either human bone marrow or human umbilical cord blood in vitro. Subsequent organ culture results in a transient production of a few CD4+ CD8+ (double-positive) cells and then the accumulation of CD4+ or CD8+ (s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.22.10778
更新日期:1993-11-15 00:00:00
abstract::Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.102163499
更新日期:2002-05-14 00:00:00
abstract::Early events in both T-cell receptor (CD3)- and CD4-induced signal transduction pathways include tyrosine phosphorylation of protein substrates, the generation of phosphatidylinositol-phosphate breakdown products, and the mobilization of intracellular Ca2+. Oxidative stress in T cells mediated by sulfhydryl-reactive n...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.1.300
更新日期:1992-01-01 00:00:00
abstract::The aggregation of the amyloid-β (Aβ) peptide is linked to the pathogenesis of Alzheimer's disease (AD). In particular, some point mutations within Aβ are associated with early-onset familial Alzheimer's disease. Here we set out to explore how the physical properties of the altered side chains, including their sizes a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1803539115
更新日期:2018-06-26 00:00:00
abstract::One of the critical issues regarding proteins with a four-helix bundle motif is which interactions play the major role in stabilizing this type of folded structure: the interaction among the four alpha-helices or the interaction between the loop and helix segments. To answer this question, an energetic analysis has be...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.16.7315
更新日期:1992-08-15 00:00:00
abstract::Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+) store depletion. Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.051632698
更新日期:2001-03-13 00:00:00
abstract::A pluripotent cell line, C3H10T1/2, is induced to undergo adipogenesis by a mixture of factors that includes a glucocorticoid such as dexamethasone. We found that expression of myostatin (MSTN), a TGF-beta family member extensively studied in muscle, was induced by dexamethasone under those differentiation conditions....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607501103
更新日期:2006-10-17 00:00:00
abstract::The complete soybean leghemoglobin lbc(3) gene was transferred into the legume Lotus corniculatus using an Agrobacterium rhizogenes vector system. Organ-specific expression of the soybean gene was observed in root nodules formed on regenerated transgenic plants after infection with Rhizobium loti. The primary transcri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.16.5754
更新日期:1987-08-01 00:00:00
abstract::Tropical forests hold most of Earth's biodiversity. Their continued loss through deforestation and agriculture is the main threat to species globally, more than disease, invasive species, and climate change. However, not all tropical forests have the same ability to sustain biodiversity. Those that have been disturbed...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809753115
更新日期:2018-11-13 00:00:00
abstract::Peptidoglycan recognition proteins (PGRPs) are highly conserved pattern-recognition molecules of the innate immune system that bind bacterial peptidoglycans (PGNs), which are polymers of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) cross-linked by short peptide stems. Human PRGPs are bactericid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0701453104
更新日期:2007-05-22 00:00:00
abstract::The regulatory mechanisms underlying the uptake and utilization of multiple types of carbohydrates in actinomycetes remain poorly understood. In this study, we show that GlnR (central regulator of nitrogen metabolism) serves as a universal regulator of nitrogen metabolism and plays an important, previously unknown rol...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1508465112
更新日期:2015-12-22 00:00:00
abstract::The E2F1 transcription factor has a well-characterized activation domain at its C terminus and the E1A protein has a recently defined activation domain at its N terminus. Here we show that these activation domains are highly related in sequence. The sequence homology reflects, at least partly, the conservation of comm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.4.1439
更新日期:1996-02-20 00:00:00
abstract::Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL) controlling resistance to trypanosomosis in cattle, an experimental cross was made between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptible im...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1232392100
更新日期:2003-06-24 00:00:00
abstract::Nucleosomes are the fundamental structural unit of chromatin. In addition to stabilizing the DNA polymer, nucleosomes are modified in ways that reflect and affect gene expression in their vicinity. It has long been assumed that nucleosomes can transmit memory of gene expression through their covalent posttranslational...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1911943116
更新日期:2019-10-08 00:00:00
abstract::Glucocorticoids are commonly used antiinflammatory agents whose use is limited by side effects. We have developed a series of glucocorticoid receptor (GR) ligands that retain the strong antiinflammatory activity of conventional glucocorticoids with reduced side effects. We present a compound, LGD5552, that binds the r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705517104
更新日期:2007-12-04 00:00:00
abstract::Sparse 3T3 cells, in excess serum, become quiescent in the early G(1) (or G(0)) phase of the cell cycle if the cells are cultured in low concentrations of amino acids, glucose, or phosphate ion. These quiescent cells then initiate DNA synthesis if the concentration of the limiting nutrient is increased. In normal medi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.8.2942
更新日期:1974-08-01 00:00:00
abstract::Promoter-proximal stalling, a general phenomenon observed during the expression of many RNA polymerase II transcribed genes, is dependent on transcription factor IIH (TFIIH). Reactions lacking TFIIH initiated transcription, but the transcription complex encountered a block to elongation proximal to the promoter. The a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.17.9767
更新日期:1998-08-18 00:00:00
abstract::The term quantum turbulence denotes the turbulent motion of quantum fluids, systems such as superfluid helium and atomic Bose-Einstein condensates, which are characterized by quantized vorticity, superfluidity, and, at finite temperatures, two-fluid behavior. This article introduces their basic properties, describes t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type:
doi:10.1073/pnas.1400033111
更新日期:2014-03-25 00:00:00
abstract::Tracheal antimicrobial peptide (TAP) is a member of the beta-defensin family of antibiotic peptides found in the tracheal mucosa of the cow. TAP gene expression in the bovine airway is inducible by lipopolysaccharide and inflammatory mediators, suggesting that it functions to protect the upper airway from infection. L...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.24.14118
更新日期:1996-11-26 00:00:00
abstract::IFN-gamma is well known as the signature cytokine of CD4+ T helper 1, CD8+, and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma exp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1332767100
更新日期:2003-06-24 00:00:00
abstract::Antigen-specific activation of T lymphocytes, via stimulation of the T-cell antigen receptor (TCR) complex, is marked by a rapid and sustained increase in the concentration of cytoplasmic free Ca2+ ([Ca2+]i). It has been suggested that the second messenger inositol 1,4,5-trisphosphate (IP3) produced after TCR stimulat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.13.6007
更新日期:1995-06-20 00:00:00
abstract::Tumor-specific molecules are needed across diverse areas of oncology for use in early detection, diagnosis, prognosis and therapy. Large and growing public databases of transcriptome sequencing data (RNA-seq) derived from tumors and normal tissues hold the potential of yielding tumor-specific molecules, but because th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1508057112
更新日期:2015-06-09 00:00:00
abstract::Completely parthenogenetic Trichogramma wasps can be rendered permanently bisexual by treatment with three different antibiotics or high temperatures. The evidence strongly suggests that maternally inherited microorganisms cause parthenogenesis in these wasps. Theories predict female-biased sex ratio in offspring unde...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.7.2424
更新日期:1990-04-01 00:00:00
abstract::Several lines of investigation suggest that the nondegradable fluorophores that accumulate as lipofuscin in retinal pigment epithelium (RPE) cells contribute to the etiology of macular degeneration. Despite evidence that much of this fluorescent material may originate as inadvertent products of the retinoid cycle, the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501266102
更新日期:2005-05-17 00:00:00