Abstract:
:Single-molecule methods have given experimental access to the mechanical properties of single protein molecules. So far, access has been limited to mostly one spatial direction of force application. Here, we report single-molecule experiments that explore the mechanical properties of a folded protein structure in precisely controlled directions by applying force to selected amino acid pairs. We investigated the deformation response of GFP in five selected directions. We found fracture forces widely varying from 100 pN up to 600 pN. We show that straining the GFP structure in one of the five directions induces partial fracture of the protein into a half-folded intermediate structure. From potential widths we estimated directional spring constants of the GFP structure and found values ranging from 1 N/m up to 17 N/m. Our results show that classical continuum mechanics and simple mechanistic models fail to describe the complex mechanics of the GFP protein structure and offer insights into the mechanical design of protein materials.
journal_name
Proc Natl Acad Sci U S Aauthors
Dietz H,Berkemeier F,Bertz M,Rief Mdoi
10.1073/pnas.0602995103subject
Has Abstractpub_date
2006-08-22 00:00:00pages
12724-8issue
34eissn
0027-8424issn
1091-6490pii
0602995103journal_volume
103pub_type
杂志文章abstract::To repurpose compounds for diffuse large B cell lymphoma (DLBCL), we screened a library of drugs and other targeted compounds approved by the US Food and Drug Administration on 9 cell lines and validated the results on a panel of 32 genetically characterized DLBCL cell lines. Dasatinib, a multikinase inhibitor, was ef...
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.1905239116
更新日期:2019-08-20 00:00:00
abstract::Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs....
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.1212811109
更新日期:2012-09-04 00:00:00
abstract::The strikingly high incidence of obstructed labor due to the disproportion of fetal size and the mother's pelvic dimensions has puzzled evolutionary scientists for decades. Here we propose that these high rates are a direct consequence of the distinct characteristics of human obstetric selection. Neonatal size relativ...
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.1612410113
更新日期:2016-12-20 00:00:00
abstract::Excellent electrophoretic separations of a variety of biological molecules can be accomplished by using uncharged, triblock copolymers as the "gel" media. These copolymers form uncrosslinked, lyotropic liquid crystalline phases of large micelles between which molecules must travel. Unlike crosslinked hydrogels in 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.95.4.1534
更新日期:1998-02-17 00:00:00
abstract::The hepatic pigment accumulated in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated rats, which has been reported to inhibit ferrochelatase, has been isolated and purified. The pigment has been resolved into one major, one minor, and two trace components, all of which appear to be isomeric porphyrins. The major fract...
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.78.3.1490
更新日期:1981-03-01 00:00:00
abstract::Growth factor-induced signals govern the expression of three D-type cyclins, which, in turn, function as regulatory subunits of cyclin-dependent kinases (cdks) to control cell cycle transitions during the late G1 interval. 32D myeloid cells, which self-renew as uncommitted precursors in interleukin 3 (IL-3), express c...
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.90.24.11513
更新日期:1993-12-15 00:00:00
abstract::Despite the common use of the blooming metaphor, its floral inspiration remains poorly understood. Here we study the physical process of blooming in the asiatic lily Lilium casablanca. Our observations show that the edges of the petals wrinkle as the flower opens, suggesting that differential growth drives the deploym...
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.1007808108
更新日期:2011-04-05 00:00:00
abstract::The Na/K pump is a P-type ATPase that exchanges three intracellular Na(+) ions for two extracellular K(+) ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na(+) or K(+); site III binds only Na(+)) are po...
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.1004214107
更新日期:2010-10-26 00:00:00
abstract::The mechanism of phospholipase C regulation by inhibitory receptors was analyzed both in intact and in permeabilized rat thyroid cells (FRTL5). In this system, the muscarinic agonist carbachol inhibited phospholipase C, as indicated by the decrease in the basal levels of inositol 1,4,5-trisphosphate as well as by 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.87.12.4889
更新日期:1990-06-01 00:00:00
abstract::There are at least three short-range gap repressors in the precellular Drosophila embryo: Krüppel, Knirps, and Giant. Krüppel and Knirps contain related repression motifs, PxDLSxH and PxDLSxK, respectively, which mediate interactions with the dCtBP corepressor protein. Here, we present evidence that Giant might also i...
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.111158298
更新日期:2001-05-22 00:00:00
abstract::Ab initio multi-reference second-order perturbation theory computations are used to explore the photochemical behavior of two ion pairs constituted by a chloride counterion interacting with either a rhodopsin or bacteriorhodopsin chromophore model (i.e., the 4-cis-gamma-methylnona-2,4,6,8-tetraeniminium and all-trans-...
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.0408723102
更新日期:2005-05-03 00:00:00
abstract::Homeostasis is indispensable to counteract the destabilizing effects of Hebbian plasticity. Although it is commonly assumed that homeostasis modulates synaptic strength, membrane excitability, and firing rates, its role at the neural circuit and network level is unknown. Here, we identify changes in higher-order netwo...
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.1918368117
更新日期:2020-09-29 00:00:00
abstract::Insects, as a group, have been remarkably successful in adapting to a great range of physical and biological environments, in large part because of their ability to fly. The evolution of flight in small insects was accompanied by striking adaptations of the thoracic musculature that enabled very high wing beat frequen...
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.0604972103
更新日期:2006-11-14 00:00:00
abstract::Elucidating the lineage relationships among different cell types is key to understanding human brain development. Here we developed parallel RNA and DNA analysis after deep sequencing (PRDD-seq), which combines RNA analysis of neuronal cell types with analysis of nested spontaneous DNA somatic mutations as cell lineag...
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.2006163117
更新日期:2020-06-23 00:00:00
abstract::A panel of rat monoclonal antibodies was used to classify mouse mast cells from four different sources on the basis of their surface determinants. Three populations of mast cells were derived by culturing normal bone marrow, spleen, and peripheral blood cells, whereas the fourth population was isolated directly from t...
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.80.19.5916
更新日期:1983-10-01 00:00:00
abstract::It is shown that polyphosphates are not generated in significant amounts in the phosphoglycerate kinase reaction; polyphosphate is more effective than ATP in the formation of glucose 6-P by glucokinase, but the rate with ATP may be adequate to meet the requirements of glucose metabolism; PPi is far more effective than...
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.82.2.312
更新日期:1985-01-01 00:00:00
abstract::A target protein for nalidixic and oxolinic acids in Escherichia coli, the nalA gene product (Pnal), was purified to homogeneity as judged by gel electrophoresis, using an in vitro complementation assay. It is a dimer of identical 110,000-dalton subunits. A polypeptide of this molecular weight is uniquely induced by 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.74.11.4767
更新日期:1977-11-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification 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.0913572107
更新日期:2010-02-09 00:00:00
abstract::Design and synthesis of 3D metallic carbon that is stable under ambient conditions has been a long-standing dream. We predict the existence of such phases, T6- and T14-carbon, consisting of interlocking hexagons. Their dynamic, mechanical, and thermal stabilities are confirmed by carrying out a variety of state-of-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.1311028110
更新日期:2013-11-19 00:00:00
abstract::Lizards and snakes putatively arose between the early Jurassic and late Triassic; they diversified worldwide and now occupy many different ecological niches, making them ideal for testing theories on the origin of ecological traits. We propose and test the "deep history hypothesis," which claims that differences in ec...
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.0501104102
更新日期:2005-05-31 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) knockout mice raised in the laboratory of Fujii-Kuriyama have been under investigation for several years because of the presence in their urinary bladder of large, yellowish stones. The stones are composed of uric acid and become apparent in the bladders as tiny stones when mice are...
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.1120581109
更新日期:2012-01-24 00:00:00
abstract::AcrAB is a constitutively expressed, major multidrug efflux system of Escherichia coli. We have purified the cytoplasmic membrane component, AcrB, to near homogeneity, and reconstituted the protein into proteoliposomes. In the presence of DeltapH (outside acid), the protein catalyzed the extrusion of fluorescent phosp...
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.96.13.7190
更新日期:1999-06-22 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disease in which genetic risk has been mapped to HLA, but precise allelic associations have been difficult to infer due to limitations in genotyping methodology. Mapping PD risk at highest possible resolution, we performed sequencing of 11 HLA genes in 1,597 PD cases and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1821778116
更新日期:2019-04-09 00:00:00
abstract::The Hairy-related transcription-factor (HRT) genes encode three related basic helix-loop-helix transcription factors that show sequence similarity to the Hairy and Enhancer of split family of transcriptional repressors. HRT proteins are expressed in specific regions of the developing heart, vasculature, pharyngeal arc...
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.250485597
更新日期:2000-12-05 00:00:00
abstract::The kinetics of the reduction of horseheart ferricytochrome c by sodium dithionite (phosphate buffer-sodium chloride; pH 6.5, mu = 1.0, 25 degrees ) features two reaction pathways; one with the rate constant k(3) = 1.17 x 10(4) M(-1) sec(-1), the other with the rate constant k(1)k(2)/k(-1) = 6.0 x 10(4) M(-1) sec(-1)....
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.70.6.1701
更新日期:1973-06-01 00:00:00
abstract::Serum provides growth factors that regulate and limit the growth of normal cells in tissue culture. Animal cells that are malignantly transformed usually exhibit diminished serum requirements for growth in culture. We have used a defined, serum-free medium to determine which of these growth factors becomes dispensable...
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.76.8.3937
更新日期:1979-08-01 00:00:00
abstract::A striking feature of the human genome is the dearth of CpG dinucleotides (CpGs) interrupted occasionally by CpG islands (CGIs), regions with relatively high content of the dinucleotide. CGIs are generally associated with promoters; genes, whose promoters are especially rich in CpG sequences, tend to be expressed in m...
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.0510310103
更新日期:2006-01-31 00:00:00
abstract::An interpretation is given of recent experiments by Brunori et al. on the binding of carbon monoxide by hemoglobin under photodissociating conditions. It is shown that their results follow directly from scalable models for hemoglobin in which the protein-modulated interactions are separable from the ligand binding. ...
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.70.3.673
更新日期:1973-03-01 00:00:00
abstract::Ca(2+) influx through L-type Ca(2+) channels (LTCCs) influences numerous physiological processes ranging from contraction in muscle and memory in neurons to gene expression in many cell types. However, the spatiotemporal organization of functional LTCCs has been nearly impossible to investigate because of methodologic...
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.0500360102
更新日期:2005-08-02 00:00:00
abstract::alpha-1-Antitrypsin is a serum protein that inhibits many proteolytic enzymes. Recently, it was suggested that the alpha-1-antitrypsin-trypsin complex is an acyl ester analogous to the acyl intermediate that forms between trypsin and its substrates. In previous work we showed that the alpha-1-antitrypsin-trypsin compl...
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.74.10.4311
更新日期:1977-10-01 00:00:00