Abstract：
:Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins2,3. How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.
journal_name
Naturejournal_title
Natureauthors
Wang L,Qian H,Nian Y,Han Y,Ren Z,Zhang H,Hu L,Prasad BVV,Laganowsky A,Yan N,Zhou Mdoi
10.1038/s41586-020-2280-2subject
Has Abstractpub_date
2020-05-01 00:00:00pages
329-332issue
7808eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2280-2journal_volume
581pub_type
杂志文章相关文献
NATURE文献大全abstract：:Fault strength is a fundamental property of seismogenic zones, and its temporal changes can increase or decrease the likelihood of failure and the ultimate triggering of seismic events. Although changes in fault strength have been suggested to explain various phenomena, such as the remote triggering of seismicity, the...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature08395
更新日期：2009-10-01 00:00:00
abstract：:The guanine nucleotide-binding stimulatory protein (Gs) couples hormone-receptor interaction to the activation of adenylate cyclase and the generation of cyclic AMP. Studies using frog neuroepithelium indicate that the sense of smell is mediated by a Gs-adenylate cyclase system, and this prompted us to test olfaction ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/322635a0
更新日期：1986-08-14 00:00:00
abstract：:MicroRNAs (miRNAs) are approximately 22-nucleotide endogenous RNAs that often repress the expression of complementary messenger RNAs. In animals, miRNAs derive from characteristic hairpins in primary transcripts through two sequential RNase III-mediated cleavages; Drosha cleaves near the base of the stem to liberate a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05983
更新日期：2007-07-05 00:00:00
abstract：:Dynamic access to genetic information is central to organismal development and environmental response. Consequently, genomic processes must be regulated by mechanisms that alter genome function relatively rapidly. Conventional chromatin immunoprecipitation (ChIP) experiments measure transcription factor occupancy, but...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10985
更新日期：2012-04-11 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 社论
doi：10.1038/d41586-018-07151-0
更新日期：2018-10-01 00:00:00
abstract：:In order to direct a movement towards a visual stimulus, visual spatial information must be combined with postural information. For example, directing gaze (eye plus head) towards a visible target requires the combination of retinal image location with eye and head position to determine the location of the target rela...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/29777
更新日期：1998-08-27 00:00:00
abstract：:The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with res...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09907
更新日期：2011-04-28 00:00:00
abstract：:Eukaryotic cells contain genes termed proto-oncogenes (c-onc) which have the potential to transform cells in culture and induce tumours in vivo. Most of these genes have been identified by their occasional incorporation into retroviral genomes which can act as natural transducing vectors for these and perhaps other ce...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/309085a0
更新日期：1984-05-03 00:00:00
abstract：:Vertical movement of the hip during locomotion causes a loaded backpack to be accelerated with each step, which imposes large peak forces on the wearer. Here we show that using bungee cords to suspend the load from a backpack frame reduces not only its vertical movement, and hence its vertical force on the carrier, bu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/4441023a
更新日期：2006-12-21 00:00:00
abstract：:Human T-cell leukaemias and lymphomas associated with the human T-cell leukaemia viruses (HTLV) are invariably neoplasms of cells with mature T-lymphocyte phenotype. Epstein-Barr virus-transformed B- lymphoycte lines which are productively infected with HTLV may be isolated from patients with HTLV malignancies, but no...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/309276a0
更新日期：1984-05-17 00:00:00
abstract：:Abiraterone blocks androgen synthesis and prolongs survival in patients with castration-resistant prostate cancer, which is otherwise driven by intratumoral androgen synthesis. Abiraterone is metabolized in patients to Δ(4)-abiraterone (D4A), which has even greater anti-tumour activity and is structurally similar to e...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature17954
更新日期：2016-05-26 00:00:00
abstract：:The gal operon of Escherichia coli is controlled by two independent promotors--one is activated and the other inhibited by cyclic AMP and cyclic AMP receptor protein. The two promotors are modulated, however, by the same operator locus and receptor protein. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/279492a0
更新日期：1979-06-07 00:00:00
abstract：:The discovery of the basis of genetic variation has opened inroads to understanding our history as a species. It has revealed the remarkable genetic similarity we share with other individuals as well as with our closest primate relatives. To understand what make us unique, both as individuals and as a species, we need...
journal_title：Nature
pub_type： 杂志文章,评审
doi：10.1038/nature01400
更新日期：2003-01-23 00:00:00
abstract：:Excitatory amino acids (EAAs) are important neurotransmitters in the vertebrate central nervous system. Electrophysiological and ligand-binding studies indicate that at least three different receptor subtypes for EAAs exist--N-methyl-D-aspartate, kainate and quisqualate receptor subtypes--on the basis of the preferred...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/342684a0
更新日期：1989-12-07 00:00:00
abstract：:The nucleotides immediately surrounding intron/exon junctions of genes transcribed by RNA polymerase B can be derived from 'consensus' sequences for donor and acceptor splice sites by only a few base changes. Studies in vivo have underlined the importance of these junction nucleotides for splicing. In higher eukaryote...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/315430a0
更新日期：1985-05-30 00:00:00
abstract：:China is the world's most populous country and a major emitter of greenhouse gases. Consequently, much research has focused on China's influence on climate change but somewhat less has been written about the impact of climate change on China. China experienced explosive economic growth in recent decades, but with only...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09364
更新日期：2010-09-02 00:00:00
abstract：:The surfaces of Earth and Mars contain large bedrock canyons that were carved by catastrophic outburst floods. Reconstructing the magnitude of these canyon-forming floods is essential for understanding the ways in which floods modify planetary surfaces, the hydrology of early Mars and abrupt changes in climate. Flood ...
journal_title：Nature
pub_type： 信件
doi：10.1038/nature19817
更新日期：2016-10-13 00:00:00
abstract：:Villin is an actin-binding protein of relative molecular mass (Mr) 95,000 found in the core bundle of microfilaments in brush border microvilli from intestine. In physiological calcium concentrations (less than 1 microM), villin crosslinks actin filaments into bundles. However, in free calcium concentrations (greater ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/315248a0
更新日期：1985-05-16 00:00:00
abstract：:Understanding the capacity of natural populations to adapt to their local environment is a central topic in evolutionary biology. Phenotypic differences between populations may have a genetic basis, but showing that they reflect different adaptive optima requires the quantification of both gene flow and selection. Goo...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature03083
更新日期：2005-01-06 00:00:00
abstract：:Attempts to inhibit the recognition of soluble antigens by T lymphocytes using antibodies specific for the antigen in question have been uniformally unsuccessful, in contrast to the observed specific inhibition of antibody generation by B cells. One exception is the unique situation whereby anti-hapten antisera inhibi...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/308547a0
更新日期：1984-04-05 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-07631-3
更新日期：2018-12-01 00:00:00
abstract：:Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle. Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature19756
更新日期：2016-09-29 00:00:00
abstract：:A connection between thunderstorms and the ionosphere has been hypothesized since the mid-1920s. Several mechanisms have been proposed to explain this connection, and evidence from modelling as well as various types of measurements demonstrate that lightning can interact with the lower ionosphere. It has been proposed...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature03638
更新日期：2005-06-09 00:00:00
abstract：:A soluble enzyme system has been discovered which specifically recognizes and replicates plasmids containing the Escherichia coli chromosomal origin, oriC. Electron microscopy has shown that plasmid replication begins at or near oriC from which it progresses bidirectionally to completion. Control of initiation of a cy...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/296623a0
更新日期：1982-04-15 00:00:00
abstract：:Transformation of the well-studied maize transposable elements into other plant species should enable transposon tagging methodology to be used for the isolation of interesting genes in the heterologous host. Here we describe the isolation of a transposon-tagged male sterile mutant in Arabidopsis thaliana using the ma...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/363715a0
更新日期：1993-06-24 00:00:00
abstract：:Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Commo...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09745
更新日期：2011-02-03 00:00:00
abstract：:Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1-3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer's disease4-6. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-03160-0
更新日期：2021-01-20 00:00:00
abstract：:During female germline development, oocytes become a highly specialized cell type and form a maternal cytoplasmic store of crucial factors. Oocyte growth is triggered at the transition from primordial to primary follicle and is accompanied by dynamic changes in gene expression1, but the gene regulatory network that co...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-3027-9
更新日期：2021-01-01 00:00:00
abstract：:The realization of superfluidity in a dilute gas of fermionic atoms, analogous to superconductivity in metals, represents a long-standing goal of ultracold gas research. In such a fermionic superfluid, it should be possible to adjust the interaction strength and tune the system continuously between two limits: a Barde...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02199
更新日期：2003-12-04 00:00:00
abstract：:In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca2+ release results in mitochondrial Ca2...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature22965
更新日期：2017-06-22 00:00:00
