Abstract:
:To study the protein structure-function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two points approximates the structural distance between their corresponding domains. We use these maps to study the spatial distributions of properties of proteins, and in particular those of local vicinities in structure space such as structural density and functional diversity. These maps provide a unique broad view of protein space and thus reveal previously undescribed fundamental properties thereof. At the same time, the maps are consistent with previous knowledge (e.g., domains cluster by their SCOP class) and organize in a unified, coherent representation previous observation concerning specific protein folds. To investigate the function-structure relationship, we measure the functional diversity (using the Gene Ontology controlled vocabulary) in local structural vicinities. Our most striking finding is that functional diversity varies considerably across structure space: The space has a highly diverse region, and diversity abates when moving away from it. Interestingly, the domains in this region are mostly alpha/beta structures, which are known to be the most ancient proteins. We believe that our unique perspective of structure space will open previously undescribed ways of studying proteins, their evolution, and the relationship between their structure and function.
journal_name
Proc Natl Acad Sci U S Aauthors
Osadchy M,Kolodny Rdoi
10.1073/pnas.1102727108subject
Has Abstractpub_date
2011-07-26 00:00:00pages
12301-6issue
30eissn
0027-8424issn
1091-6490pii
1102727108journal_volume
108pub_type
杂志文章abstract::Methods are described for the removal of the sporophytic pollen grain coating of Brassica oleracea and for the isolation of coat polypeptides. The coat contains a small number of proteins ranging from 6 to 45 kDa. Many of the larger proteins are glycosylated, while all carry high positive charges resulting in pI value...
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.90.2.467
更新日期:1993-01-15 00:00:00
abstract::MicroRNAs (miRNAs) are small (approximately 21 nt), noncoding RNAs that negatively regulate target mRNAs at the posttranscriptional level that are involved in development. In plants, virus-induced disease symptoms often result in developmental abnormalities resembling perturbation of miRNA-mediated function. Here, we ...
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.0504439102
更新日期:2005-07-19 00:00:00
abstract::A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyncratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein sequences to circumvent ...
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.92.26.11993
更新日期:1995-12-19 00:00:00
abstract::A two-dimensional model of the expansion of a crack in an elastic medium is considered in which friction depends on the slip rate and the modulus of cohesion depends on the speed of expansion of the crack. Elastic waves are neglected (quasi-static model). Under some conditions, the expansion of the crack is realized 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.78.9.5284
更新日期:1981-09-01 00:00:00
abstract::In previous work we identified a basilar papilla protein (BPP23) that appears to be one of the most abundant soluble proteins in the basilar papilla of the chick cochlea. Here we report the purification of protein BPP23 from chick cochlea and the generation of a specific antiserum. Immunoblotting and immunoprecipitati...
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.85.10.3387
更新日期:1988-05-01 00:00:00
abstract::In vitro and in vivo triplet state electron paramagnetic resonance (epr) spectra of bacteriochlorophylls (Bchls) show important differences in (a) electron spin polarization (esp), and (b) zero field splitting (ZFS) parameters. The unusual esp and ZFS properties of the observed in vivo triplet state are best interpret...
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.72.9.3270
更新日期:1975-09-01 00:00:00
abstract::DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes). The aim of the present study was to define the structural relationship between the site(s) of covalently bound interc...
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.190312697
更新日期:2000-09-26 00:00:00
abstract::Mechanical stability in many biological materials is provided by the crosslinking of large structural proteins with gamma-glutamyl-epsilon-lysyl amide bonds. The three-dimensional structure of human recombinant factor XIII (EC 2.3.2.13 zymogen; protein-glutamine:amine gamma-glutamyltransferase a chain), a transglutami...
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.91.15.7296
更新日期:1994-07-19 00:00:00
abstract::Light chain allotypic determinants were demonstrated on the surface of peripheral blood lymphocytes of rabbits. By means of a combined immunofluorescent and autoradiographic technique, a great majority of the individual lymphocytes of rabbits heteroxygous at the b locus were shown to have detectable quantities of only...
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.68.2.430
更新日期:1971-02-01 00:00:00
abstract::Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly ...
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.1420369111
更新日期:2014-12-16 00:00:00
abstract::Infection of newborn rats with Borne disease virus (BDV) results in selective degeneration of granule cell neurons of the dentate gyrus (DG). To study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this BDV-induced neuronal degeneration. To this end, we infected ...
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.1214939110
更新日期:2013-01-29 00:00:00
abstract::Receptor-binding specificity of HA, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Influenza type B virus almost exclusively infects humans and contributes to the annual "flu" sickness. Here we report the structures of influenza B virus HA in complex ...
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.0708363104
更新日期:2007-10-23 00:00:00
abstract::Bacteriophage display of antibodies provides a method for the generation of immunological reagents against rare and uncharacterized antigens. To ascertain the usefulness of this approach for the characterization of inner-ear proteins, we produced a bacteriophage-displayed antibody-fragment library directed against pro...
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.030535797
更新日期:2000-02-29 00:00:00
abstract::Influenza viruses contain segmented, negative-strand RNA genomes. Genome segmentation facilitates reassortment between different influenza virus strains infecting the same cell. This phenomenon results in the rapid exchange of RNA segments. In this study, we have developed a method to prevent the free reassortment 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.0908897106
更新日期:2009-09-15 00:00:00
abstract::Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells ...
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.75.4.1805
更新日期:1978-04-01 00:00:00
abstract::The "false thumb" of pandas is a carpal bone, the radial sesamoid, which has been enlarged and functions as an opposable thumb. If the giant panda (Ailuropoda melanoleuca) and the red panda (Ailurus fulgens) are not closely related, their sharing of this adaptation implies a remarkable convergence. The discovery of pr...
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.0504899102
更新日期:2006-01-10 00:00:00
abstract::Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by defects of the ventral midline, including hypertelorism, cleft lip and palate, heart defects, and mental retardation. We recently identified the gene responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a member of 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.96.6.2794
更新日期:1999-03-16 00:00:00
abstract::Isolated human erythrocyte spectrin is a dimer of two unique polypeptide chains. The dimer (alpha beta) undergoes reversible salt- and temperature-dependent association to form (alpha beta)2 tetramers. Spectrin also binds with high affinity to a protein receptor on the cytoplasmic surface of erythrocyte membrane vesic...
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.77.11.6592
更新日期:1980-11-01 00:00:00
abstract::Whereas the laws of thermodynamics prohibit extraction of useful work from the Brownian motion of particles in equilibrium, these motions can be "rectified" under nonequilibrium conditions, for example, in the presence of asymmetric geometrical obstacles. Here, we describe a class of systems in which aerobic bacteria ...
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.0913015107
更新日期:2010-01-19 00:00:00
abstract::Anti-idiotype antibodies (Ab2) were purified from a cancer patient treated with NP-4, a murine monoclonal antibody to carcinoembryonic antigen (CEA). These Ab2 were specific for NP-4 and inhibited the binding between NP-4 and CEA. BALB/c mice immunized with these human Ab2 produced anti-Ab2 antibodies that were also 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.88.8.3421
更新日期:1991-04-15 00:00:00
abstract::At meiotic prophase, chromatin loops around a proteinaceous core, with the sizes of these loops varying between species. Comparison of the morphology of sequence-related inserts at different sites in transgenic mice demonstrates that loop size also varies with chromosomal geography. Similarly, chromatin loop lengths 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.93.7.2795
更新日期:1996-04-02 00:00:00
abstract::CCAAT/enhancer binding protein (C/EBP) epsilon is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin. The human C/EBPepsilon gene is transcribed by two alternative promoters, Palpha and Pbeta. A combination of differential splicing and al...
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.94.12.6462
更新日期:1997-06-10 00:00:00
abstract::The product of the Escherichia coli secB gene is required for efficient export of proteins across the cytoplasmic membrane. The studies described in this report show that in wild-type growing cells, SecB protein associates with precursor forms of exported proteins, such as the periplasmic maltose-binding protein (MBP)...
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.86.14.5320
更新日期:1989-07-01 00:00:00
abstract::Remarkable progress has come from whole-brain models linking anatomy and function. Paradoxically, it is not clear how a neuronal dynamical system running in the fixed human anatomical connectome can give rise to the rich changes in the functional repertoire associated with human brain function, which is impossible to ...
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.1921475117
更新日期:2020-04-28 00:00:00
abstract::The breast and ovarian cancer suppressor BRCA2 controls the enzyme RAD51 during homologous DNA recombination (HDR) to preserve genome stability. BRCA2 binds to RAD51 through 8 conserved BRC repeat motifs dispersed in an 1127-residue region (BRCA2([BRC1-8])). Here, we show that BRCA2([BRC1-8]) exerts opposing effects 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.0906208106
更新日期:2009-08-11 00:00:00
abstract::2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling...
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.2003434117
更新日期:2020-07-07 00:00:00
abstract::No microorganism capable of anaerobic growth on methane as the sole carbon source has yet been cultivated. Consequently, information about these microbes has been inferred from geochemical and microbiological observations of field samples. Stable isotope analysis of lipid biomarkers and rRNA gene surveys have implicat...
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.072210299
更新日期:2002-05-28 00:00:00
abstract::NADH:quinone oxidoreductase (complex I) plays a pivotal role in cellular energy production. It employs a series of redox cofactors to couple electron transfer to the generation of a proton-motive force across the inner mitochondrial or bacterial cytoplasmic membrane. Complex I contains a noncovalently bound flavin mon...
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.0705593104
更新日期:2007-07-31 00:00:00
abstract::We show that the stimulation of human immunodeficiency virus (HIV) brought about by tumor necrosis factor alpha and phorbol 12-myristate 13-acetate can be inhibited by adding N-acetyl-L-cysteine (NAC). NAC, which replenishes intracellular glutathione, effectively inhibits the tumor necrosis factor alpha- or phorbol es...
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.87.12.4884
更新日期:1990-06-01 00:00:00
abstract::AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target 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.1405186111
更新日期:2014-08-05 00:00:00