Abstract：
:Stearoyl-CoA desaturase (SCD) is conserved in all eukaryotes and introduces the first double bond into saturated fatty acyl-CoAs. Because the monounsaturated products of SCD are key precursors of membrane phospholipids, cholesterol esters and triglycerides, SCD is pivotal in fatty acid metabolism. Humans have two SCD homologues (SCD1 and SCD5), while mice have four (SCD1-SCD4). SCD1-deficient mice do not become obese or diabetic when fed a high-fat diet because of improved lipid metabolic profiles and insulin sensitivity. Thus, SCD1 is a pharmacological target in the treatment of obesity, diabetes and other metabolic diseases. SCD1 is an integral membrane protein located in the endoplasmic reticulum, and catalyses the formation of a cis-double bond between the ninth and tenth carbons of stearoyl- or palmitoyl-CoA. The reaction requires molecular oxygen, which is activated by a di-iron centre, and cytochrome b5, which regenerates the di-iron centre. To understand better the structural basis of these characteristics of SCD function, here we crystallize and solve the structure of mouse SCD1 bound to stearoyl-CoA at 2.6 Å resolution. The structure shows a novel fold comprising four transmembrane helices capped by a cytosolic domain, and a plausible pathway for lateral substrate access and product egress. The acyl chain of the bound stearoyl-CoA is enclosed in a tunnel buried in the cytosolic domain, and the geometry of the tunnel and the conformation of the bound acyl chain provide a structural basis for the regioselectivity and stereospecificity of the desaturation reaction. The dimetal centre is coordinated by a unique spacial arrangement of nine conserved histidine residues that implies a potentially novel mechanism for oxygen activation. The structure also illustrates a possible route for electron transfer from cytochrome b5 to the di-iron centre.
journal_name
Naturejournal_title
Natureauthors
Bai Y,McCoy JG,Levin EJ,Sobrado P,Rajashankar KR,Fox BG,Zhou Mdoi
10.1038/nature14549subject
Has Abstractpub_date
2015-08-13 00:00:00pages
252-6issue
7564eissn
0028-0836issn
1476-4687pii
nature14549journal_volume
524pub_type
杂志文章相关文献
NATURE文献大全abstract：:The way in which proteins attain and maintain their final form is of fundamental importance. Recent work has focused on the role of a set of ubiquitous proteins, termed chaperonins, in the assembly of phage and multisubunit proteins. The range of chaperonin action is unknown; they could interact with most cellular pol...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/342451a0
更新日期：1989-11-23 00:00:00
abstract：:The Tharsis region is the largest volcanic complex on Mars and in the Solar System. Young lava flows cover its surface (from the Amazonian period, less than 3 billion years ago) but its growth started during the Noachian era (more than 3.7 billion years ago). Its position has induced a reorientation of the planet with...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature17171
更新日期：2016-03-17 00:00:00
abstract：:Hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) produces two prospective intracellular messengers: inositol 1,4,5-trisphosphate (InsP3), which releases Ca2+ from intracellular stores; and diacylglycerol (DG), which activates protein kinase C. Here we show how the formation...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/323333a0
更新日期：1986-09-25 00:00:00
abstract：:Strong interactions between electrons in a solid material can lead to surprising properties. A prime example is the Mott insulator, in which suppression of conductivity occurs as a result of interactions rather than a filled Bloch band. Proximity to the Mott insulating phase in fermionic systems is the origin of many ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07244
更新日期：2008-09-11 00:00:00
abstract：:Four incorrect figure citations in this Letter have been corrected online. ...
journal_title：Nature
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41586-018-0560-x
更新日期：2018-11-01 00:00:00
abstract：:Photosynthetic dinoflagellates are important aquatic primary producers and notorious causes of toxic 'red tides'. Typical dinoflagellate chloroplasts differ from all other plastids in having a combination of three envelope membranes and peridinin-chlorophyll a/c light-harvesting pigments. Despite evidence of a dinofla...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/22099
更新日期：1999-07-08 00:00:00
abstract：:Mammalian circadian clocks consist of complex integrated feedback loops that cannot be elucidated without comprehensive measurement of system dynamics and determination of network structures. To dissect such a complicated system, we took a systems-biological approach based on genomic, molecular and cell biological tec...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature00906
更新日期：2002-08-01 00:00:00
abstract：:Mechanical milling is an effective technique for the preparation of fine metallic and ceramic powders and can also be used to drive a wide range of chemical reactions. Milling devices include planetary machines, attritors and vibrational mills; products include amorphous, nanocrystalline and quasicrystalline materials...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature00985
更新日期：2002-09-12 00:00:00
abstract：:Recognition of a functional 3' splice site in pre-mRNA splicing requires a heterodimer of the proteins U2AF65/U2AF35. U2AF65 binds to RNA at the polypyrimidine tract, whereas U2AF35 is thought to interact through its arginine/serine-rich (RS) domain with other RS-domain-containing factors bound at the 5' splice site, ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/41137
更新日期：1997-07-24 00:00:00
abstract：:The three-dimensional structure of the 67K amino-terminal fragment of Escherichia coli DNA topoisomerase I has been determined to 2.2 A resolution. The polypeptide folds in an unusual way to give four distinct domains enclosing a hole large enough to accommodate a double-stranded DNA. The active-site tyrosyl residue, ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/367138a0
更新日期：1994-01-13 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：:Leukaemia inhibitory factor (LIF) has a variety of effects on different cell types in vitro, inhibiting the differentiation of embryonic stem cells and promoting the survival and/or proliferation of primitive haematopoietic precursors and primordial germ cells. Here we show that LIF-deficient mice derived by gene targ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/363361a0
更新日期：1993-05-27 00:00:00
abstract：:In addition to coordinating immune and inflammatory responses, NF-kappaB/Rel transcription factors control cell survival. Normally, NF-kappaB dimers are sequestered in the cytoplasm by binding to inhibitory IkappaB proteins, and can be activated rapidly by signals that induce the sequential phosphorylation and proteol...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35104560
更新日期：2001-11-15 00:00:00
abstract：:Considerable attention has centered recently on the changes in neuron excitability and synaptic efficacy caused by certain biogenic amines and neuropeptides. These neuromodulators act at a wide variety of both central and peripheral targets, and bring about diverse biological results. In sensory pathways, modulation o...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/326793a0
更新日期：1987-04-23 00:00:00
abstract：:Splicing of the Tetrahymena ribosomal intron was first studied by Cech et al., who subsequently demonstrated that the intron RNA catalyses its own excision from a primary transcript to yield mature ribosomal RNA. This intron shares several short conserved sequences and a common secondary structure with several other i...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/322083a0
更新日期：1986-07-03 00:00:00
abstract：:A pathological hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of amyloid fibrils is beta/A4 amyloid protein, which can be generated by the aberrant processing of a large membrane-bound glycoprotein, the beta/A4 amyloid protein precursor (APP)3. To test whethe...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/359064a0
更新日期：1992-09-03 00:00:00
abstract：:A putative growth hormone receptor from rabbit liver and the growth hormone binding protein from rabbit serum have the same amino-terminal amino-acid sequence, indicating that the binding protein corresponds to the extracellular hormone-binding domain of the liver receptor. The complete amino-acid sequences derived fr...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/330537a0
更新日期：1987-12-10 00:00:00
abstract：:The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment (a process required for cell division), but the molecular mechanism underlying its function remains unknown. Here we present a subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09423
更新日期：2010-10-14 00:00:00
abstract：:The Gulf Stream transports approximately 31 Sv (1 Sv = 10(6) m(3) s(-1)) of water and 1.3 x 10(15) W of heat into the North Atlantic ocean. The possibility of abrupt changes in Gulf Stream heat transport is one of the key uncertainties in predictions of climate change for the coming centuries. Given the limited length...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05277
更新日期：2006-11-30 00:00:00
abstract：:Understanding the physical mechanisms behind the generation of ocean waves by wind has been a longstanding challenge. Previous studies have assumed that ocean waves induce fluctuations in velocity and pressure of the overlying air that are synchronized with the waves, and numerical models have supported this assumptio...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01382
更新日期：2003-03-06 00:00:00
abstract：:Disruption of the normal regulation of cell-cycle progression and division lies at the heart of the events leading to cancer. Complex networks of regulatory factors, the tumour microenvironment and stress signals, such as those resulting from damaged DNA, dictate whether cancer cells proliferate or die. Recent progres...
journal_title：Nature
pub_type： 杂志文章,评审
doi：10.1038/nature03095
更新日期：2004-11-18 00:00:00
abstract：:Data from a rocket experiment show details which were not known from ground-based observations. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/226526a0
更新日期：1970-05-09 00:00:00
abstract：:Chick embryo fibroblasts (CEF) infected with avian sarcoma virus become rapidly transformed as a result of expression of the viral src gene in the form of a single polypeptide of molecular weight 60,000 (pp60src) with protein kinase activity and suggested preferential association with the plasma membrane. Studies with...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/287241a0
更新日期：1980-09-18 00:00:00
abstract：:The activation of T cells through interaction of their T-cell receptors with antigenic peptide bound to major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a crucial step in adaptive immunity. Here we use three-dimensional fluorescence microscopy to visualize individual peptide-...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01076
更新日期：2002-10-24 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-07372-3
更新日期：2018-12-01 00:00:00
abstract：:Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins. However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable. Here, using advances in computational proteom...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07341
更新日期：2008-10-30 00:00:00
abstract：:Mineral nitrogen in nature is often found in the form of nitrate (NO3(-)). Numerous microorganisms evolved to assimilate nitrate and use it as a major source of mineral nitrogen uptake. Nitrate, which is central in nitrogen metabolism, is first reduced to nitrite (NO2(-)) through a two-electron reduction reaction. The...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature12139
更新日期：2013-05-30 00:00:00
abstract：:The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtaine...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05972
更新日期：2007-07-12 00:00:00
abstract：:Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest known relatives are the rickettsial group of alpha-proteobacteria. Because characterized mitochondrial genomes vary markedly in structure, it has been impossible to i...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/387493a0
更新日期：1997-05-29 00:00:00
abstract：:The terminal differentiation of myogenic cells initiates in the proximal portion of the limb bud whereas the distal region remains undifferentiated and proliferative. The apical ectodermal ridge maintains the progress zone in an undifferentiated state and induces proliferation of limb mesenchymal cells. Hox-7.1, a hom...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/360477a0
更新日期：1992-12-03 00:00:00
