Abstract:
:The monomeric VDAC channel shows an accelerated pH titration of its transport properties with a Hill coefficient of about 2. This manifests itself as a sharp peak in conductance noise as well as a fast change in channel selectivity with pH. On the basis of the known structure of this channel, we propose that this cooperativity arises from a mechanically linked mobile pair of ionizable groups. Concerted movement of these groups between two states changes the distance from nearby electrostatic charge to influence the pK of the groups. This model of pH-dependent motion produces positive cooperative behavior that fits the observations without need for subunits or identifiable domains within the protein. The mathematical formalism has never required such domains, but these are generally considered an essential part of cooperative behavior in proteins. The present proposal reduces the size of a cooperative unit to a minimum, extending the limits of what is perceived to be possible. Together with large-scale conformational transitions, these subtle cooperative structural changes may allow proteins to adapt, with high sensitivity, to changes in their environment. They might also be relatively easy to engineer into a protein.
journal_name
Proc Natl Acad Sci U S Aauthors
Rostovtseva TK,Liu TT,Colombini M,Parsegian VA,Bezrukov SMdoi
10.1073/pnas.140115397keywords:
subject
Has Abstractpub_date
2000-07-05 00:00:00pages
7819-22issue
14eissn
0027-8424issn
1091-6490pii
140115397journal_volume
97pub_type
杂志文章abstract::The nucleotide and predicted amino acid sequences of two variant cDNAs [rat brain thyroid hormone receptor (rTR alpha) vI and vII], isolated from a rat brain cDNA library by using the Pst I fragment of v-erbA, showed virtual identity with the rat brain thyroid hormone receptor (rTR alpha) [Thompson, C. C., Weinberger,...
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.85.16.5804
更新日期:1988-08-01 00:00:00
abstract::GPIbalpha binding to von Willebrand factor (VWF) exposed at a site of vascular injury is thought to be the first step in the formation of a hemostatic plug. However, our previous studies in VWF-deficient mice demonstrated delayed but not absent arterial thrombus formation, suggesting that, under these conditions, GPIb...
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.0608207103
更新日期:2006-11-07 00:00:00
abstract::The solar system formed from interstellar dust and gas in a molecular cloud. Astronomical observations show that typical interstellar dust consists of amorphous (a-) silicate and organic carbon. Bona fide physical samples for laboratory studies would yield unprecedented insight about solar system formation, but they 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.1720167115
更新日期:2018-06-26 00:00:00
abstract::Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei x B6.129S7-Ldlr(tm1Her)) x C57BL/6J-Ldlr(tm1Her) backcross mice, homozygous for the Ldl...
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.141239098
更新日期:2001-07-03 00:00:00
abstract::Vascular endothelial cells (ECs) at arterial branches and curvatures experience disturbed blood flow and induce a quiescent-to-activated phenotypic transition of the adjacent smooth muscle cells (SMCs) and a subsequent smooth muscle hyperplasia. However, the mechanism underlying the flow pattern-specific initiation of...
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.1700561114
更新日期:2017-08-01 00:00:00
abstract::The gene encoding the receptor for hyaluronan-mediated motility (RHAMM) is overexpressed in many human cancers. However, it is unclear whether RHAMM plays a causal role in tumor initiation or progression. Using somatic gene transfer in a mouse model of islet cell tumorigenesis, we demonstrate that RHAMM isoform B (RHA...
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.1114022108
更新日期:2011-10-04 00:00:00
abstract::IL-17 is a T cell-derived, proinflammatory cytokine that is suspected to be involved in the development of various inflammatory diseases. Although there are elevated levels of IL-17 in synovial fluid of patients with rheumatoid arthritis, the pathogenic role of IL-17 in the development of rheumatoid arthritis remains ...
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.1035999100
更新日期:2003-05-13 00:00:00
abstract::Although preterm delivery is a major global health issue, its causes and underlying mechanism remain elusive. Using mutant mice, mimicking aspects of human preterm birth, we show here that uterine decidual senescence early in pregnancy via heightened mammalian target of rapamycin complex 1 (mTORC1) signaling is a sign...
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.1108180108
更新日期:2011-11-01 00:00:00
abstract::The nature of color categories in the world's languages is contested. One major view holds that color categories are organized around universal focal colors, whereas an opposing view holds instead that categories are defined at their boundaries by linguistic convention. Both of these standardly opposed views are chall...
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.0610341104
更新日期:2007-01-23 00:00:00
abstract::Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of ...
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.97.9.4926
更新日期:2000-04-25 00:00:00
abstract::G-protein-coupled receptors (GPCRs) are key signaling molecules and are intensely studied. Whereas GPCRs recognizing small-molecules have been successfully targeted for drug discovery, protein-recognizing GPCRs, such as the chemokine receptors, claim few drugs or even useful small molecule reagents. This reflects both...
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.1120431109
更新日期:2012-04-03 00:00:00
abstract::A dinuclear nickel complex with methyl and thiolate ligands, Ni(dadt(Et))Ni(Me)(SDmp) (2), has been synthesized as a dinuclear Ni(d)-Ni(p)-site model of acetyl-CoA synthase (ACS) (dadt(Et) is N,N'-diethyl-3,7-diazanonane-1,9-dithiolate; Dmp is 2,6-dimesitylphenyl). Complex 2 was prepared via 2 methods: (i) ligand subs...
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.0900433106
更新日期:2009-07-21 00:00:00
abstract::The results of normal-mode analyses are in accord with the proposal that a low-frequency motion of the HhaI methyltransferase enzyme is responsible for base flipping in bound DNA. The vectors of the low-frequency normal mode of residues Ser-85 and Ile-86 point directly to the phosphate and ribose moieties of the DNA b...
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.0507913102
更新日期:2005-11-08 00:00:00
abstract::Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback-controlled confinement of single cells 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.1502029112
更新日期:2015-09-08 00:00:00
abstract::Calendar date of the beginning of the growing season at high altitude in the Colorado Rocky Mountains is variable but has not changed significantly over the past 25 years. This result differs from growing evidence from low altitudes that climate change is resulting in a longer growing season, earlier migrations, 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.97.4.1630
更新日期:2000-02-15 00:00:00
abstract::The SKW-3 cell line, which was established from the malignant cells of a patient with T-cell chronic lymphocytic leukemia, is characterized by a translocation involving chromosome 8 (band q24) and chromosome 14 (band q11) [t(8;14)(q24;q11)]. To determine the position of the gene encoding the alpha chain of the T-cell ...
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.83.10.3439
更新日期:1986-05-01 00:00:00
abstract::The defining feature of the mycobacterial outer membrane (OM) is the presence of mycolic acids (MAs), which, in part, render the bilayer extremely hydrophobic and impermeable to external insults, including many antibiotics. Although the biosynthetic pathway of MAs is well studied, the mechanism(s) by which these lipid...
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.1700062114
更新日期:2017-07-25 00:00:00
abstract::We have isolated an Arabidopsis thaliana gene that codes for a receptor related to antifungal pathogenesis-related (PR) proteins. The PR5K gene codes for a predicted 665-amino acid polypeptide that comprises an extracellular domain related to the PR5 proteins, a central transmembrane-spanning domain, and an intracellu...
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.93.6.2598
更新日期:1996-03-19 00:00:00
abstract::The DNA polymerase enzymes from avian, murine, and feline RNA tumor viruses can be distinguished by their ability to read specific, synthetic primertemplates. The copying of templates containing adenylic and thymidylic acids by all these DNA polymerases is inhibited by ethidium bromide, though this compound affects 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.68.12.3116
更新日期:1971-12-01 00:00:00
abstract::Measurements of submicron particles by Fourier transform infrared spectroscopy in 14 campaigns in North America, Asia, South America, and Europe were used to identify characteristic organic functional group compositions of fuel combustion, terrestrial vegetation, and ocean bubble bursting sources, each of which often ...
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.1006461108
更新日期:2011-03-01 00:00:00
abstract::Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic ...
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.081275298
更新日期:2001-04-24 00:00:00
abstract::A number of distressing trends, including a decline in the share of key research grants going to younger scientists, as well as a steady rise in the age at which investigators receive their first funding, are now a decades-long feature of the US biomedical research workforce. Working committees have proposed recommend...
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.1418761112
更新日期:2015-01-13 00:00:00
abstract::Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microsc...
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.1222824110
更新日期:2013-05-28 00:00:00
abstract::Aminoacyl-tRNA synthetases (amino acid-tRNA ligases, EC 6.1.1.-) catalyze the aminoacylation of specific amino acids onto their cognate tRNAs with extraordinary accuracy. Recent reports, however, indicate that this class of enzymes may play other roles in cellular metabolism. Several aminoacyl-tRNA synthetases are her...
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.84.22.7891
更新日期:1987-11-01 00:00:00
abstract::Helicobacter pylori is a Gram-negative bacterial pathogen with a small genome of 1.64-1.67 Mb. More than 20 putative DNA restriction-modification (R-M) systems, comprising more than 4% of the total genome, have been identified in the two completely sequenced H. pylori strains, 26695 and J99, based on sequence similari...
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.051612298
更新日期:2001-02-27 00:00:00
abstract::Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian syste...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1516953113
更新日期:2016-03-08 00:00:00
abstract::Estrogen receptors (ERs) are believed to be ligand-activated transcription factors belonging to the nuclear receptor superfamily, which on ligand binding translocate into the nucleus and activate gene transcription. To date, two ERs have been identified: ERalpha and ERbeta. ERalpha plays major role in the estrogen-med...
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.0306948101
更新日期:2004-03-23 00:00:00
abstract::Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription f...
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.1614412114
更新日期:2017-03-14 00:00:00
abstract::A 2.9-kilobase Acc I fragment of the DNA of the pneumococcal bacteriophage Cp-1, containing the cpl gene, hybridizes with the lytA gene encoding the pneumococcal amidase. The nucleotide sequence of the cpl gene of Cp-1, encoding a muramidase (CPL), has been determined. The 3' regions of the cpl and lytA coding sequenc...
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.85.3.914
更新日期:1988-02-01 00:00:00
abstract::Factor VIII (antihemophilic factor) is a high molecular weight plasma glycoprotein that participates in the blood clotting cascade. The recent cloning and sequence analysis of the cDNA encoding human factor VIII revealed an obvious domain structure for the protein, which can be represented as A1-A2-B-A3-C1-C2. We now ...
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.83.16.5939
更新日期:1986-08-01 00:00:00