Abstract:
:Application of hydrostatic pressure shifts protein conformational equilibria in a direction to reduce the volume of the system. A current view is that the volume reduction is dominated by elimination of voids or cavities in the protein interior via cavity hydration, although an alternative mechanism wherein cavities are filled with protein side chains resulting from a structure relaxation has been suggested [López CJ, Yang Z, Altenbach C, Hubbell WL (2013) Proc Natl Acad Sci USA 110(46):E4306-E4315]. In the present study, mechanisms for elimination of cavities under high pressure are investigated in the L99A cavity mutant of T4 lysozyme and derivatives thereof using site-directed spin labeling, pressure-resolved double electron-electron resonance, and high-pressure circular dichroism spectroscopy. In the L99A mutant, the ground state is in equilibrium with an excited state of only ∼ 3% of the population in which the cavity is filled by a protein side chain [Bouvignies et al. (2011) Nature 477(7362):111-114]. The results of the present study show that in L99A the native ground state is the dominant conformation to pressures of 3 kbar, with cavity hydration apparently taking place in the range of 2-3 kbar. However, in the presence of additional mutations that lower the free energy of the excited state, pressure strongly populates the excited state, thereby eliminating the cavity with a native side chain rather than solvent. Thus, both cavity hydration and structure relaxation are mechanisms for cavity elimination under pressure, and which is dominant is determined by details of the energy landscape.
journal_name
Proc Natl Acad Sci U S Aauthors
Lerch MT,López CJ,Yang Z,Kreitman MJ,Horwitz J,Hubbell WLdoi
10.1073/pnas.1506505112subject
Has Abstractpub_date
2015-05-12 00:00:00pages
E2437-46issue
19eissn
0027-8424issn
1091-6490pii
1506505112journal_volume
112pub_type
杂志文章abstract::Although much is known about the underlying mechanisms of p53 activity and regulation, the factors that influence the diversity and duration of p53 responses are not well understood. Here we describe a unique mode of p53 regulation involving alternative splicing of the TP53 gene. We found that the use of an alternativ...
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.1321640111
更新日期:2014-08-12 00:00:00
abstract::Pregnant mothers often report a special awareness of and bonding with their unborn child. Little is known about this relationship although it may offer potential for the assessment of the fetal condition. Recently we found evidence of short epochs of fetal-maternal heart rate synchronization under uncontrolled conditi...
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.0901049106
更新日期:2009-08-18 00:00:00
abstract::A vaccine capable of stimulating protective antiviral antibody responses is needed to curtail the global AIDS epidemic caused by HIV-1. Although rarely elicited during the course of natural infection or upon conventional vaccination, the membrane-proximal ectodomain region (MPER) of the HIV-1 glycoprotein of M(r) 41,0...
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.0901474106
更新日期:2009-06-02 00:00:00
abstract::Two photochromic activators of the electrogenic membrane of the electroplax of Electrophorus electricus are described. Trans-3,3'-bis[alpha-(trimethylammonium)methyl]azobenzene dibromide (Bis-Q), one of the most potent ever reported, is active at concentrations of less than 10(-7) M. Its cis isomer, which is obtained ...
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.68.8.1820
更新日期:1971-08-01 00:00:00
abstract::The DNA sequence of a tryptophan synthase gene and the flanking 5' and 3' regions has been determined for Arabidopsis thaliana. The sequence encodes only the beta subunit domain, indicating that alpha and beta subunits are specified by separate genes. The gene contains four introns and encodes 470 amino acid residues....
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.86.12.4604
更新日期:1989-06-01 00:00:00
abstract::Ca2+, pheromones, sweet taste compounds, and the main neurotransmitters glutamate and gamma-aminobutyric acid activate G protein-coupled receptors (GPCRs) that constitute the GPCR family 3. These receptors are dimers, and each subunit has a large extracellular domain called a Venus flytrap module (VFTM), where agonist...
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.162138699
更新日期:2002-08-20 00:00:00
abstract::Superficial cells from early amphibian embryos display regional specializations of their cell surfaces. That portion of the plasma membrane facing the perivitelline space (apical surface) is nonadhesive, whereas, in the same cell, the lateral and basal portions of the plasma membrane will adhere to other cells. These ...
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.77.6.3460
更新日期:1980-06-01 00:00:00
abstract::Peritoneal macrophages were obtained from DBA/2 mice that were untreated or after the injection of bacillus Calmette-Guerin (BCG), thioglycollate broth, proteose-peptone broth, or gamma-irradiated P-815 tumor cells. These macrophages were "activated" to become cytotoxic for a fibroblast cell line (L 929) by the additi...
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.80.7.2031
更新日期:1983-04-01 00:00:00
abstract::Cell cycle checkpoints appear to contribute to an increase in cell survival and a decrease in abnormal heritable genetic changes following exposure to DNA damaging agents. Though several radiation-sensitive yeast mutants have been identified, little is known about the genes that control these responses in mammalian ce...
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.89.16.7491
更新日期:1992-08-15 00:00:00
abstract::Rapid development of genetic variability may contribute to the pathogenicity of lentiviruses as it may allow escape from immune surveillance and/or from suppression of virus replication. Although apathogenic in African green monkeys, simian immunodeficiency virus isolated from African green monkeys is shown to display...
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.88.18.8126
更新日期:1991-09-15 00:00:00
abstract::We developed a "continual engagement" model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundar...
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.0900313106
更新日期:2016-04-26 00:00:00
abstract::The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte p...
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.1635050100
更新日期:2003-09-30 00:00:00
abstract::Development of type 1 diabetes in the nonobese diabetic (NOD) mouse is preceded by an immune cell infiltrate in the pancreatic islets. The exact role of the attracted cells is still poorly understood. Chemokine CCL2/MCP-1 is known to attract CCR2(+) monocytes and dendritic cells (DCs). We have previously shown that tr...
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.1115308109
更新日期:2012-02-28 00:00:00
abstract::Intracisternal A-particles were isolated from three different myeloma lines in BALB/c mice and from cultured neuroblastoma cells of A/J origin. All preparations contained a major structural protein with an apparent molecular weight near 70,000 as estimated by electrophoretic mobility in sodium dodecyl sulfate-containi...
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.69.1.218
更新日期:1972-01-01 00:00:00
abstract::Sympatric speciation (SS), i.e., speciation within a freely breeding population or in contiguous populations, was first proposed by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection] and is still controversial despite theoretical support [Gavrilets S (2004) Fitness Landscapes and the Orig...
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.1514896112
更新日期:2015-09-22 00:00:00
abstract::Ocean acidification (OA) refers to the ongoing decline in oceanic pH resulting from the uptake of atmospheric CO(2). Mounting experimental evidence suggests that OA will have negative consequences for a variety of marine organisms. Whereas the effect of OA on the calcification of adult reef corals is increasingly well...
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.1007273107
更新日期:2010-11-23 00:00:00
abstract::An electrophoretically slow albumin variant was detected with a phenotype frequency of about 1:1000 in Sweden and was also found in a family of Scottish descent from Kaikoura, New Zealand, and in five families in Tradate, Italy. Structural study established that the major variant component was arginyl-albumin, in whic...
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.87.10.3909
更新日期:1990-05-01 00:00:00
abstract::Groundwater-dependent species are among the least-known components of global biodiversity, as well as some of the most vulnerable because of rapid groundwater depletion at regional and global scales. The karstic Edwards-Trinity aquifer system of west-central Texas is one of the most species-rich groundwater systems in...
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.1815014116
更新日期:2019-02-12 00:00:00
abstract::A systematic comparison of crystal structures of nine different B-DNA dodecamers, in three different space groups, with and without A-tracts, shows that crystal packing or lattice forces are of secondary importance for helix axis bending, minor-groove width, and propeller twist. While other local helix parameters may ...
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.91.9.3579
更新日期:1994-04-26 00:00:00
abstract::Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for 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.0609708104
更新日期:2007-04-03 00:00:00
abstract::The Arabidopsis thaliana SOS2 and SOS3 genes are required for intracellular Na(+) and K(+) homeostasis and plant tolerance to high Na(+) and low K(+) environments. SOS3 is an EF hand type calcium-binding protein having sequence similarities with animal neuronal calcium sensors and the yeast calcineurin B. SOS2 is a se...
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.040577697
更新日期:2000-03-28 00:00:00
abstract::The basic helix-loop-helix transcriptional repressor Hairy-related transcription factor 2 (Hrt2) is expressed in ventricular, but not atrial, cardiomyocytes, and in endothelial and vascular smooth muscle cells. Mice homozygous for a null mutation of Hrt2 die perinatally from a spectrum of cardiac abnormalities, raisin...
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.0702447104
更新日期:2007-05-08 00:00:00
abstract::The configurations of the hydrocarbon chains in micelles are severely constrained by the space-filling requirements of the chain segments, by the continuity of the chains, and by the micellar geometry. A statistical theory that takes full account of these constraints is developed by using a lattice model. The chain en...
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.78.2.676
更新日期:1981-02-01 00:00:00
abstract::p-Coumaric acid is the precursor of phenylpropanoids, which are plant secondary metabolites that are beneficial to human health. Tyrosine ammonia lyase catalyzes the production of p-coumaric acid from tyrosine. Because of their photosynthetic ability and biosynthetic versatility, cyanobacteria are promising candidates...
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.1323725111
更新日期:2014-07-01 00:00:00
abstract::Modulation of gene expression by steroid hormones is mediated by receptor proteins that associate with regulatory elements of responsive genes upon binding the hormone ligand. The finding that two glucocorticoid responsive elements act cooperatively to stimulate transcription of the tyrosine aminotransferase gene prom...
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.85.20.7526
更新日期:1988-10-01 00:00:00
abstract::Characterizing the entropy of a system is a crucial, and often computationally costly, step in understanding its thermodynamics. It plays a key role in the study of phase transitions, pattern formation, protein folding, and more. Current methods for entropy estimation suffer from a high computational cost, lack of gen...
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.2017042117
更新日期:2020-12-01 00:00:00
abstract::Prenatal unilateral enucleation in mammals causes an extensive anatomical reorganization of visual pathways. The remaining eye innervates the entire extent of visual subcortical and cortical areas. Electrophysiological recordings have shown that the retino-geniculate connections are retinotopically organized and genic...
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.90.23.11142
更新日期:1993-12-01 00:00:00
abstract::The ever-increasing industrial demand for nylon-6 (polycaprolactam) necessitates the development of environmentally benign methods of producing its precursor, epsilon-caprolactam, from cyclohexanone. It is currently manufactured in two popular double-step processes, each of which uses highly aggressive reagents, and e...
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.0506907102
更新日期:2005-09-27 00:00:00
abstract::RNA of a common strain of tobacco mosaic virus was sequentially reconstituted first with protein of the same strain and then with protein of a tomato strain. The reconstituted particles were treated with specific antibodies against the two strain particles and were examined electron microscopically to locate the regio...
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.74.5.1913
更新日期:1977-05-01 00:00:00
abstract::It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, w...
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.84.13.4636
更新日期:1987-07-01 00:00:00