Abstract:
:Ankyrin-G (AnkG), a highly enriched scaffold protein in the axon initial segment (AIS) of neurons, functions to maintain axonal polarity and the integrity of the AIS. At the AIS, AnkG regulates selective intracellular cargo trafficking between soma and axons via interaction with the dynein regulator protein Ndel1, but the molecular mechanism underlying this binding remains elusive. Here we report that Ndel1's C-terminal coiled-coil region (CT-CC) binds to giant neuron-specific insertion regions present in both AnkG and AnkB with 2:1 stoichiometry. The high-resolution crystal structure of AnkB in complex with Ndel1 CT-CC revealed the detailed molecular basis governing the AnkB/Ndel1 complex formation. Mechanistically, AnkB binds with Ndel1 by forming a stable 5-helix bundle dominated by hydrophobic interactions spread across 6 distinct interaction layers. Moreover, we found that AnkG is essential for Ndel1 accumulation at the AIS. Finally, we found that cargo sorting at the AIS can be disrupted by blocking the AnkG/Ndel1 complex formation using a peptide designed based on our structural data. Collectively, the atomic structure of the AnkB/Ndel1 complex together with studies of cargo sorting through the AIS establish the mechanistic basis for AnkG/Ndel1 complex formation and for the maintenance of axonal polarity. Our study will also be valuable for future studies of the interaction between AnkB and Ndel1 perhaps at distal axonal cargo transport.
journal_name
Proc Natl Acad Sci U S Aauthors
Ye J,Li J,Ye F,Zhang Y,Zhang M,Wang Cdoi
10.1073/pnas.1916987117subject
Has Abstractpub_date
2020-01-14 00:00:00pages
1207-1215issue
2eissn
0027-8424issn
1091-6490pii
1916987117journal_volume
117pub_type
杂志文章abstract::In signal-recognition particle (SRP)-dependent protein targeting to the bacterial plasma membrane, two GTPases, Ffh (a subunit of the bacterial SRP) and FtsY (the bacterial SRP receptor), act as GTPase activating proteins for one another. The molecular mechanism of this reciprocal GTPase activation is poorly understoo...
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.0737693100
更新日期:2003-04-15 00:00:00
abstract::The genome of a thermophilic fungus, Thermomyces lanuginosus, contains a tandemly arranged cluster of sequences that are approximately equal to 50% homologous with the cytoplasmic 5S RNA and that are selectable by hybridization techniques. Unlike typical pseudogenes, these sequences are not truncated; rather, they bea...
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.81.6.1768
更新日期:1984-03-01 00:00:00
abstract::The matrix-2 (M2) protein from influenza A virus is a tetrameric, integral transmembrane (TM) protein that plays a vital role in viral replication by proton flux into the virus. The His37 tetrad is a pH sensor in the center of the M2 TM helix that activates the channel in response to the low endosomal pH. M2 consists ...
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.1913385117
更新日期:2020-02-18 00:00:00
abstract::The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recentl...
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.1018878108
更新日期:2011-02-08 00:00:00
abstract::The voltage-gated potassium (Kv) channel Kv1.5 mediates the I(Kur) repolarizing current in human atrial myocytes and regulates vascular tone in multiple peripheral vascular beds. Understanding the complex regulation of Kv1.5 function is of substantial interest because it represents a promising pharmacological target f...
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.0606702104
更新日期:2007-02-06 00:00:00
abstract::Pronounced bright and dark bands are seen at the bright and dark edges of half-shadows and similar distributions of illumination. These are the so-called Mach bands. A pair of vertical Mach bands was generated with a ramp pattern in the central strip of a horizontal tripartite oscilloscope display. This pattern consis...
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.80.14.4554
更新日期:1983-07-01 00:00:00
abstract::We are interested in using recombinant adeno-associated viral vectors in the treatment of hemophilia A. Because of the size constraints of recombinant adeno-associated viral vectors, we delivered the heavy and light chains of the human factor 8 (hFVIII) cDNA independently by using two separate vectors. Recombinant AAV...
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.96.22.12725
更新日期:1999-10-26 00:00:00
abstract::The tongue is a critical element of the feeding system in tetrapod animals for their successful adaptation to terrestrial life. Whereas the oral part of the mammalian tongue contains soft tissues only, the avian tongue has an internal skeleton extending to the anterior tip. The mechanisms underlying the evolutionary 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.1306495110
更新日期:2013-11-12 00:00:00
abstract::In a recently discovered class of oncogenes, GTPase-inhibiting mutations constitutively activate alpha subunits of signal-transducing guanine nucleotide-binding proteins (G proteins). Somatic mutations in a subclass of endocrine tumors are found in the arginine-179 codon of the alpha subunit of Gi2 (alpha i2), creatin...
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.88.16.7031
更新日期:1991-08-15 00:00:00
abstract::Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin filaments elongate and are knitted together into higher-order 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.1314138111
更新日期:2014-02-11 00:00:00
abstract::IL-17A is a therapeutic target in many autoimmune diseases. Most nonhematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing proinflammatory cytokines. The IL-17A signal transduction triggers two broad, TRAF6- and TRAF5-dependent, intracellular signaling pathways to produce represen...
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.2008214117
更新日期:2020-10-06 00:00:00
abstract::The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly und...
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.1616363114
更新日期:2017-04-04 00:00:00
abstract::In flowering plants, the asymmetrical division of the zygote is the first hallmark of apical-basal polarity of the embryo and is controlled by a MAP kinase pathway that includes the MAPKKK YODA (YDA). In Arabidopsis, YDA is activated by the membrane-associated pseudokinase SHORT SUSPENSOR (SSP) through an unusual pare...
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.1815866116
更新日期:2019-03-19 00:00:00
abstract::A genomic clone of one member of the Arabidopsis thaliana (L.) Heynh. 1-aminocyclopropane-1-carboxylate (ACC) synthase (S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14) gene family (AT-ACC1) was isolated and sequenced. A region of homology was found in the 5'-untranslated region with the promoter of a z...
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.89.20.9969
更新日期:1992-10-15 00:00:00
abstract::Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine secretion and function as mediators of cellular or humoral immunity, respectively. Cytokines also regulate the differentiation of Th cells. For example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development, suggesting that IL-...
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.92.15.6847
更新日期:1995-07-18 00:00:00
abstract::Expression of amino acid biosynthesis genes in bacteria is often repressed when abundant supplies of the cognate amino acid are available. Repression of the Bacillus subtilis lysC gene by lysine was previously shown to occur at the level of premature termination of transcription. In this study we show that lysine dire...
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.2133705100
更新日期:2003-10-14 00:00:00
abstract::Ceramide, a lipid mediator, has been most closely associated with antiproliferative activities. In this study, we examine the mechanism by which ceramide induces growth suppression and the role of the retinoblastoma gene product (Rb) in this process. Withdrawal of serum from the serum-dependent MOLT-4 cells resulted 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.92.5.1347
更新日期:1995-02-28 00:00:00
abstract::The lamB protein, the receptor for phage lambda, was purified from the outer membrane of Escherichia coli K-12 by extraction with Triton X-100 and EDTA, chromatography on DEAE-Sephacel in Triton X-100, exchange of Triton for cholate by gel filtration, and chromatography on Sephacryl S-200 in cholate, NaCl, and EDTA. 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.77.1.167
更新日期:1980-01-01 00:00:00
abstract::Increased clouds and precipitation normally decrease the diurnal temperature range (DTR) and thus have commonly been offered as explanation for the trend of reduced DTR observed for many land areas over the last several decades. Observations show, however, that the DTR was reduced most in dry regions and especially in...
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.0700290104
更新日期:2007-11-13 00:00:00
abstract::Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder α-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector adm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究
doi:10.1073/pnas.1617726114
更新日期:2017-02-14 00:00:00
abstract::Establishment of loss-of-function phenotypes is often a key step in determining the biological function of a gene. We describe a procedure to obtain mutant petunia plants in which a specific gene with known sequence is inactivated by the transposable element dTph1. Leaves are collected from batches of 1000 plants with...
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.92.18.8149
更新日期:1995-08-29 00:00:00
abstract::Lipoproteins are emulsion particles that consist of lipids and apolipoproteins. Their natural function is to transport lipids and/or cholesterol to different tissues. We have taken advantage of the hydrophobic interior of these natural emulsions to solubilize DNA. Negatively charged DNA was first complexed with cation...
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.94.26.14547
更新日期:1997-12-23 00:00:00
abstract::Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins apo-A-I and apoA-II in patients with Tangier disease are ap...
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.79.8.2485
更新日期:1982-04-01 00:00:00
abstract::Neonatal ablation of the suprachiasmatic nucleus in the rat has two important consequences. First, the direct projection from the retina to the suprachiasmatic nucleus fails to develop and no other retinal projection to any hypothalamic nucleus is formed. Second, circadian rhythms in drinking and spontaneous locomotor...
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.75.12.6243
更新日期:1978-12-01 00:00:00
abstract::Rhizobia colonize their legume hosts by different modes of entry while initiating symbiotic nitrogen fixation. Most legumes are invaded via growing root hairs by the root hair-curl mechanism, which involves epidermal cell responses. However, invasion of a number of tropical legumes happens through fissures at lateral ...
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.0401540101
更新日期:2004-04-20 00:00:00
abstract::Engaging mammalian Toll-like receptors (TLRs) activate both the NF-kappaB and mitogen-activated protein kinase signaling pathways. Here we establish that mitogen-activated protein 3 kinase Tpl2, levels of which are markedly reduced in nfkb1(-/-) cells, is required for extracellular signal-regulated kinase (ERK) activa...
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.0511113103
更新日期:2006-02-28 00:00:00
abstract::The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, 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.97.10.5440
更新日期:2000-05-09 00:00:00
abstract::SecA, the translocation ATPase in Escherichia coli, undergoes cycles of conformational changes (insertion/deinsertion) in response to ATP and a preprotein. The membrane-embedded portion of protein translocase, SecYEG, has crucial roles in the SecA-driven preprotein translocation reaction. We previously identified a se...
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.95.23.13567
更新日期:1998-11-10 00:00:00
abstract::One of the ultimate objectives of de novo protein design is to realize systems capable of catalyzing redox reactions on substrates. This goal is challenging as redox-active proteins require design considerations for both the reduced and oxidized states of the protein. In this paper, we describe the spectroscopic chara...
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.1212893110
更新日期:2012-12-26 00:00:00
abstract::The global financial crisis has precipitated an increasing appreciation of the need for a systemic perspective toward financial stability. For example: What role do large banks play in systemic risk? How should capital adequacy standards recognize this role? How is stability shaped by concentration and diversification...
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.1213767109
更新日期:2012-11-06 00:00:00