Abstract:
:Blood coagulation can be initiated when factor VII or VIIa, a plasma protease, binds to its essential cofactor, tissue factor (TF), and proteolytically activates factors IX and X, triggering a cascade of events which eventually leads to the formation of thrombin and a fibrin clot. Plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inhibits activated factor X (Xa) directly and, in a Xa-dependent way, inhibits VII(a)/TF activity, presumably by forming a quaternary Xa/LACI/VII(a)/TF complex. Sequence analysis of complementary DNA clones has shown that LACI contains three tandemly repeated Kunitz-type serine protease inhibitory domains. To investigate the relationship between these Kunitz structures and LACI function, we have used site-directed mutagenesis to produce altered forms of LACI in which the residue at the active-site cleft of each Kunitz domain has been individually changed. The second Kunitz domain is required for efficient binding and inhibition of Xa, and both Kunitz domains 1 and 2 are required for the inhibition of VIIa/TF activity; but alteration of the active-site residue of the third Kunitz domain has no significant effect on either function. We propose that in the putative inhibitory complex, Kunitz domain 1 is bound to the active site of VII(a)/TF and that Kunitz domain 2 is bound to Xa's active site.
journal_name
Naturejournal_title
Natureauthors
Girard TJ,Warren LA,Novotny WF,Likert KM,Brown SG,Miletich JP,Broze GJ Jrdoi
10.1038/338518a0subject
Has Abstractpub_date
1989-04-06 00:00:00pages
518-20issue
6215eissn
0028-0836issn
1476-4687journal_volume
338pub_type
杂志文章相关文献
NATURE文献大全abstract::The mobilization of aluminium from acidic forest soils is arguably the most ecologically important consequence of acid deposition in the environment because of its adverse effects on soils, forest vegetation and surface water. Here we show that there has been a significant decline in the concentrations of aluminium sp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/417242a
更新日期:2002-05-16 00:00:00
abstract::Successful expression of genes transferred into distantly related species in which genetic functions have been maintained through evolution has been reported previously. In the case of the silkmoth Bombyx mori and the fruitfly Drosophila melanogaster, both of which produce chorions (eggshells), Bombyx chorion genes ar...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/346480a0
更新日期:1990-08-02 00:00:00
abstract::Therapies for patients with cancer have changed gradually over the past decade, moving away from the administration of broadly acting cytotoxic drugs towards the use of more-specific therapies that are targeted to each tumour. To facilitate this shift, tests need to be developed to identify those individuals who requi...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature06915
更新日期:2008-04-03 00:00:00
abstract::The architecture of trabecular bone, the porous bone found in the spine and at articulating joints, provides the requirements for optimal load transfer, by pairing suitable strength and stiffness to minimal weight according to rules of mathematical design. But, as it is unlikely that the architecture is fully pre-prog...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35015116
更新日期:2000-06-08 00:00:00
abstract::Apoptosis in the immune system is a fundamental process regulating lymphocyte maturation, receptor repertoire selection and homeostasis. Thus, death by apoptosis is as essential for the function of lymphocytes as growth and differentiation. This article focuses on death receptor-associated apoptosis and the role of CD...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/35037728
更新日期:2000-10-12 00:00:00
abstract::Receptors for excitatory amino acids in the mammalian central nervous system are classified into three major subtypes, ones which prefer N-methyl-D-aspartate (NMDA), quisqualate (QA), or kainate (KA) as type agonists respectively. These receptors are considered to mediate fast postsynaptic potentials by activating ion...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325531a0
更新日期:1987-02-05 00:00:00
abstract::Molecular-scale manipulation of electronic and ionic charge accumulation in materials is the backbone of electrochemical energy storage1-4. Layered van der Waals (vdW) crystals are a diverse family of materials into which mobile ions can electrochemically intercalate into the interlamellar gaps of the host atomic latt...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0205-0
更新日期:2018-06-01 00:00:00
abstract::When a force deforms an elastic object, practical experience suggests that the resulting displacement will be in the same direction as the force. This property is known as positive stiffness. Less familiar is the concept of negative stiffness, where the deforming force and the resulting displacement are in opposite di...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35069035
更新日期:2001-03-29 00:00:00
abstract::The observation that a few species in ecological communities are exceptionally abundant, whereas most are rare, prompted the development of species abundance models. Nevertheless, despite the large literature on the commonness and rarity of species inspired by these pioneering studies, some widespread empirical patter...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01547
更新日期:2003-04-17 00:00:00
abstract::The population vector hypothesis was introduced almost twenty years ago to illustrate that a population vector constructed from neural activity in primary motor cortex (MI) of non-human primates could predict the direction of hand movement during reaching. Alternative explanations for this population signal have been ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35093102
更新日期:2001-09-13 00:00:00
abstract::The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus)...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328539a0
更新日期:1987-08-06 00:00:00
abstract::Brevetoxin A is the most potent neurotoxin secreted by Gymnodinium breve Davis, a marine organism often associated with harmful algal blooms known as 'red tides'. The compound, whose mechanism of action involves binding to and opening of sodium channels, is sufficiently toxic to kill fish at concentrations of nanogram...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/32623
更新日期:1998-03-19 00:00:00
abstract::Is the big-bang hot, warm or cold? And are galactic masses determined by the interplay of gravitational and strong interactions in the very early universe? ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/228258a0
更新日期:1970-10-17 00:00:00
abstract::The identification of properties that contribute to the persistence and resilience of ecosystems despite climate change constitutes a research priority of global relevance. Here we present a novel, empirical approach to assess the relative sensitivity of ecosystems to climate variability, one property of resilience th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16986
更新日期:2016-03-10 00:00:00
abstract::We have postulated that an excitatory postsynaptic potential (e.p.s.p.) may open voltage-sensitive K+ ('M') channels, in an appropriate depolarizing range, and that this could alter the e.p.s.p. waveform. Consequently, the fast e.p.s.p. in neurones of sympathetic ganglia, elicited by a nicotinic action of acetylcholin...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/305148a0
更新日期:1983-09-08 00:00:00
abstract::The Altai region of Siberia was inhabited for parts of the Pleistocene by at least two groups of archaic hominins-Denisovans and Neanderthals. Denisova Cave, uniquely, contains stratified deposits that preserve skeletal and genetic evidence of both hominins, artefacts made from stone and other materials, and a range o...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/s41586-018-0843-2
更新日期:2019-01-01 00:00:00
abstract::Transcription initiation factor TFIID is a multisubunit complex containing a TATA-box-binding factor (TFIID tau/TBP) and associated polypeptide factors (TAFs) with sizes ranging from M(r) approximately 20,000 to > 200,000. As a result of direct promoter interactions, TFIID nucleates the assembly of RNA polymerase II a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/367484a0
更新日期:1994-02-03 00:00:00
abstract::The role of the cytoskeleton during viral infection is poorly understood. Here we show, using a combination of mutant and drug studies, that the intracellular enveloped form of vaccinia virus is capable of inducing the formation of actin tails that are strikingly similar to those seen in Listeria, Shigella and Rickett...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/378636a0
更新日期:1995-12-07 00:00:00
abstract::Nuclear pore complexes (NPCs) fuse the inner and outer membranes of the nuclear envelope. They comprise hundreds of nucleoporins (Nups) that assemble into multiple subcomplexes and form large central channels for nucleocytoplasmic exchange1,2. How this architecture facilitates messenger RNA export, NPC biogenesis and ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2670-5
更新日期:2020-10-01 00:00:00
abstract::DNA sequences containing the 5'-flanking regions of the insulin and chymotrypsin genes were linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. The insulin gene recombinant elicits preferential expression of CAT activity when introduced into cells producing insulin; similarly, the chymot...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306557a0
更新日期:1983-12-08 00:00:00
abstract::Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest tha...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature20412
更新日期:2016-11-10 00:00:00
abstract::Fast radio bursts are mysterious millisecond-duration transients prevalent in the radio sky. Rapid accumulation of data in recent years has facilitated an understanding of the underlying physical mechanisms of these events. Knowledge gained from the neighbouring fields of gamma-ray bursts and radio pulsars has also of...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/s41586-020-2828-1
更新日期:2020-11-01 00:00:00
abstract::The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a la...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature20566
更新日期:2016-12-01 00:00:00
abstract::Blood production is ensured by rare, self-renewing haematopoietic stem cells (HSCs). How HSCs accommodate the diverse cellular stresses associated with their life-long activity remains elusive. Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11895
更新日期:2013-02-21 00:00:00
abstract::Scientific theories of how subduction and plate tectonics began on Earth--and what the tectonic structure of Earth was before this--remain enigmatic and contentious. Understanding viable scenarios for the onset of subduction and plate tectonics is hampered by the fact that subduction initiation processes must have bee...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature15752
更新日期:2015-11-12 00:00:00
abstract::A review of fossil mammalian faunas from the Middle Awash indicates they span most of the later Neogene and document evolutionary change in several mammalian groups, especially Primates, Proboscidea and Artiodactyla. Oldowan artefacts first appear in the late Pliocene, while Acheulian and later industries and apparent...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/298025a0
更新日期:1982-07-01 00:00:00
abstract::The promoter for a weakly expressed constitutive gene, the lactose repressor gene (lacI), has been sequenced, along with an 'up' promoter mutation Iq. The 10-fold enhancement in I expression found in Iq is the result of a single base change at position -35. To facilitate the sequencing, the lacI gene was cloned in a s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/274762a0
更新日期:1978-08-24 00:00:00
abstract::For hundreds of years, scientists have tracked the changing appearance of Mars, first by hand drawings and later by photographs. Because of this historical record, many classical albedo patterns have long been known to shift in appearance over time. Decadal variations of the martian surface albedo are generally attrib...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05718
更新日期:2007-04-05 00:00:00
abstract::Since the original work on Bose-Einstein condensation1,2, the use of quantum degenerate gases of atoms has enabled the quantum emulation of important systems in condensed matter and nuclear physics, as well as the study of many-body states that have no analogue in other fields of physics3. Ultracold molecules in the m...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2141-z
更新日期:2020-04-01 00:00:00
abstract::In their investigation into whether female mate-choice drives male dispersal, Höner et al. argue that female spotted hyaenas (Crocuta crocuta) prefer mates whose tenure in the social group is less than the females' age, to avoid paternal incest, and suggest that male dispersal reflects this preference. However, we are...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature07122
更新日期:2008-07-10 00:00:00