Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation

2013 ◽  
Vol 25 (12) ◽  
pp. 2702-2708 ◽  
Author(s):  
Leanne E. Wybenga-Groot ◽  
C. Jane McGlade
Keyword(s):  
Crystal Structure ◽  
Close Association ◽  
Adaptor Protein ◽  
Sh2 Domains ◽  
Β Sheet

scholarly journals Crystal structure of phosphoribulokinase from Synechococcus sp. strain PCC 6301

2019 ◽  
Vol 75 (4) ◽  
pp. 278-289 ◽  
Author(s):  
Robert H. Wilson ◽  
Manajit Hayer-Hartl ◽  
Andreas Bracher
Keyword(s):  
Crystal Structure ◽  
Disulfide Bond ◽  
Carbon Fixation ◽  
Adaptor Protein ◽  
Structural Basis ◽  
Dimer Interface ◽  
Synechococcus Sp ◽  
Β Sheet ◽  
Loop Residue

Phosphoribulokinase (PRK) catalyses the ATP-dependent phosphorylation of ribulose 5-phosphate to give ribulose 1,5-bisphosphate. Regulation of this reaction in response to light controls carbon fixation during photosynthesis. Here, the crystal structure of PRK from the cyanobacterium Synechococcus sp. strain PCC 6301 is presented. The enzyme is dimeric and has an α/β-fold with an 18-stranded β-sheet at its core. Interestingly, a disulfide bond is found between Cys40 and the P-loop residue Cys18, revealing the structural basis for the redox inactivation of PRK activity. A second disulfide bond appears to rigidify the dimer interface and may thereby contribute to regulation by the adaptor protein CP12 and glyceraldehyde-3-phosphate dehydrogenase.

scholarly journals Sec1p and Mso1p C-terminal tails cooperate with the SNAREs and Sec4p in polarized exocytosis

2011 ◽  
Vol 22 (2) ◽  
pp. 230-244 ◽  
Author(s):  
Marion Weber-Boyvat ◽  
Nina Aro ◽  
Konstantin G. Chernov ◽  
Tuula Nyman ◽  
Jussi Jäntti
Keyword(s):  
Close Association ◽  
Adaptor Protein ◽  
Binding Mode ◽  
Snare Complex ◽  
Bimolecular Fluorescence Complementation ◽  
Rab Gtpase ◽  
Temperature Sensitive ◽  
Nucleotide Exchange ◽  
Protein Receptor

The Sec1/Munc18 protein family members perform an essential, albeit poorly understood, function in association with soluble n-ethylmaleimide sensitive factor adaptor protein receptor (SNARE) complexes in membrane fusion. The Saccharomyces cerevisiae Sec1p has a C-terminal tail that is missing in its mammalian homologues. Here we show that deletion of the Sec1p tail (amino acids 658–724) renders cells temperature sensitive for growth, reduces sporulation efficiency, causes a secretion defect, and abolishes Sec1p-SNARE component coimmunoprecipitation. The results show that the Sec1p tail binds preferentially ternary Sso1p-Sec9p-Snc2p complexes and it enhances ternary SNARE complex formation in vitro. The bimolecular fluorescence complementation (BiFC) assay results suggest that, in the SNARE-deficient sso2–1 Δsso1 cells, Mso1p, a Sec1p binding protein, helps to target Sec1p(1–657) lacking the C-terminal tail to the sites of secretion. The results suggest that the Mso1p C terminus is important for Sec1p(1–657) targeting. We show that, in addition to Sec1p, Mso1p can bind the Rab-GTPase Sec4p in vitro. The BiFC results suggest that Mso1p acts in close association with Sec4p on intracellular membranes in the bud. This association depends on the Sec4p guanine nucleotide exchange factor Sec2p. Our results reveal a novel binding mode between the Sec1p C-terminal tail and the SNARE complex, and suggest a role for Mso1p as an effector of Sec4p.

scholarly journals AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A

2017 ◽  
Author(s):  
Alexandra K. Davies ◽  
Daniel N. Itzhak ◽  
James R. Edgar ◽  
Tara L. Archuleta ◽  
Jennifer Hirst ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Close Association ◽  
Adaptor Protein ◽  
Cell Types ◽  
Subcellular Localisation ◽  
Cell Periphery ◽  
Accessory Proteins ◽  
Unknown Aetiology ◽  
Spatial Control ◽  
Cargo Proteins

AbstractAdaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including ‘Dynamic Organellar Maps’, to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2. We demonstrate that AP-4 deficiency causes missorting of ATG9A in diverse cell types, including patient-derived cells, as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the TGN to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the “ATG9A reservoir” required for autophagosome biogenesis. Our study uncovers ATG9A trafficking as a ubiquitous function of the AP-4 pathway. Furthermore, it provides a potential molecular pathomechanism of AP-4 deficiency, through dysregulated spatial control of autophagy.

Crystal structure of the kelch domain of human keap1

2005 ◽  
Author(s):  
◽  
Xuchu Li
Keyword(s):  
Crystal Structure ◽  
Structural Integrity ◽  
Redox Homeostasis ◽  
Signal Transduction Pathway ◽  
Adaptor Protein ◽  
University Of Missouri ◽  
Ubiquitin Ligase Complex ◽  
Kelch Domain ◽  
High Resolution Structure ◽  
Steady State Levels

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Nrf2-Keap1 signal transduction pathway senses oxidative stress and protects eukaryotic cells against oxidative damage and cancer. The transcription factor Nrf2 induces Phase II stress response genes, which enable cells to neutralize reactive molecules and restore cellular redox homeostasis. Keap1 is a BTBKelch protein that regulates both the subcellular localization and steady state levels of Nrf2. Recently our lab has identified Keap1 as a redox-regulated substrate adaptor protein for a Cullin3-dependent E3 ubiquitin ligase complex, which targets Nrf2 for degradation in a controlled manner. The research project presented in this dissertation is to study the interaction between Nrf2 and Keap1 starting from a structural biology approach. The N-terminal Neh2 domain of Nrf2 mediates binding of Nrf2 to the Kelch domain of Keap1. We solved the crystal structure of the Kelch domain of human Keap1 and carried out detailed analysis of the structural/solvent features in this domain. This domain structure, which was the first high-resolution structure of a mammalian Kelch domain, demonstrated that the Kelch domain of Keap1 is a six-bladed ?-propeller that uses a C-terminal mode of closure. The structure revealed how conserved amino acids and water molecules contribute to both inter- and intra-blade stability and provided insight into how disease-causing mutations perturb the structural integrity of the Kelch domain. We found that the bottom loops of the Kelch domain are critical for its sufficient association with the Neh2 domain. Based on mutagenesis data, we mapped out a Neh2-Kelch interface on the bottom side of the Kelch domain. We further crystallized a putative Kelch-Neh2 complex that diffracts to 4[angstrom]. We are now in the process of obtaining high quality crystals of the Neh2-Kelch complex for structure determination purpose.--From public.pdf

scholarly journals Atomic structures of the RNA end-healing 5′-OH kinase and 2′,3′-cyclic phosphodiesterase domains of fungal tRNA ligase: conformational switches in the kinase upon binding of the GTP phosphate donor

2019 ◽  
Author(s):  
Ankan Banerjee ◽  
Yehuda Goldgur ◽  
Beate Schwer ◽  
Stewart Shuman
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Fungal Pathogens ◽  
Pathogenic Fungus ◽  
Atomic Structures ◽  
Polynucleotide Kinase ◽  
Phosphate Donor ◽  
Guanine Base ◽  
Conformational Switches ◽  
Β Sheet

Abstract Fungal tRNA ligase (Trl1) rectifies RNA breaks with 2′,3′-cyclic-PO4 and 5′-OH termini. Trl1 consists of three catalytic modules: an N-terminal ligase (LIG) domain; a central polynucleotide kinase (KIN) domain; and a C-terminal cyclic phosphodiesterase (CPD) domain. Trl1 enzymes found in all human fungal pathogens are untapped targets for antifungal drug discovery. Here we report a 1.9 Å crystal structure of Trl1 KIN-CPD from the pathogenic fungus Candida albicans, which adopts an extended conformation in which separate KIN and CPD domains are connected by an unstructured linker. CPD belongs to the 2H phosphotransferase superfamily by dint of its conserved central concave β sheet and interactions of its dual HxT motif histidines and threonines with phosphate in the active site. Additional active site motifs conserved among the fungal CPD clade of 2H enzymes are identified. We present structures of the Candida Trl1 KIN domain at 1.5 to 2.0 Å resolution—as apoenzyme and in complexes with GTP•Mg2+, IDP•PO4, and dGDP•PO4—that highlight conformational switches in the G-loop (which recognizes the guanine base) and lid-loop (poised over the nucleotide phosphates) that accompany nucleotide binding.

scholarly journals APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl

Leukemia ◽  
1999 ◽  
Vol 13 (5) ◽  
pp. 760-767 ◽  
Author(s):  
T Wakioka ◽  
A Sasaki ◽  
K Mitsui ◽  
M Yokouchi ◽  
A Inoue ◽  
...  
Keyword(s):  
Adaptor Protein ◽  
Pleckstrin Homology ◽  
Sh2 Domains ◽  
Src Homology 2 ◽  
Src Homology ◽  
Stat Pathway

Crystal structure of tert.-butyloxycarbonyl-L-prolyl-D-alanyl-D-alanyl-N-methylamide Dimeric β-sheet formation

2009 ◽  
Vol 39 (5) ◽  
pp. 458-463 ◽  
Author(s):  
V.S. ANANTHANARAYANAN ◽  
GASTON BOULAY ◽  
J. SAHAYA MARY ◽  
E. SUBRAMANIAN ◽  
ANDRÉ G. MICHEL
Keyword(s):  
Crystal Structure ◽  
Β Sheet

Badakhshanite-(Y), Y2Mn4Al(Si2B7BeO24), a new mineral species of the perettiite group from a granite miarolic pegmatite in Eastern Pamir, the Gorno Badakhshan Autonomous Oblast, Tajikistan

2020 ◽  
Vol 58 (3) ◽  
pp. 381-394
Author(s):  
Leonid A. Pautov ◽  
Mirak A. Mirakov ◽  
Fernando Cámara ◽  
Elena Sokolova ◽  
Frank C. Hawthorne ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Close Association ◽  
Coarse Grained ◽  
New Mineral ◽  
Orthorhombic Space Group ◽  
Calculated Density ◽  
Conchoidal Fracture ◽  
New Mineral Species ◽  
Mohs Hardness ◽  
Cation Sites

ABSTRACT Badakhshanite-(Y), ideally Y2Mn4Al(Si2B7BeO24), is a tetrahedral sheet-structure mineral found in the Dorozhny (Road) miarolitic granitic pegmatite within the Kukurt pegmatite field 45 km E of Murghab, Eastern Pamir, Gorno-Badakhshan Autonomous Oblast, Tajikistan. Badakhshanite-(Y) occurs in medium- to coarse-grained non-graphic albite-microcline-quartz pegmatites in close association with smoky quartz, Sc-bearing spessartine, Sc-bearing tusionite, and schorl. It often grows together with Sc-bearing tusionite and occurs as single columnar crystals ranging from 50 to 400 μm in length, as inclusions in spessartine and tourmaline, and rarely as crystals in blebs along boundaries between garnet, tourmaline, and quartz. Badakhshanite-(Y) is yellow brown and has a white streak and a vitreous luster. It is brittle, with a conchoidal fracture, Mohs hardness of 6.5–7, and calculated density of 4.41 g/cm. In thin section it is transparent and pale yellow, non-pleochroic, biaxial (–), with α = 1.805(2), βcalc = 1.827, γ = 1.835(3) (λ = 590 nm); 2V (meas.) = –60(10)°. Dispersion is weak, r > v. Extinction is straight, elongation is negative. FTIR spectra show the absence of (OH) and H2O groups. Chemical analysis by electron microprobe using WDS (6 points), SIMS, and ICP-OES for B and Be gave SiO2 11.96, ThO2 0.12, Sm2O3 0.17, Gd2O3 0.30, Tb2O3 0.10, Dy2O3 0.73, Ho2O3 0.19, Er2O3 1.34, Tm2O3 0.54, Yb2O3 8.82, Lu2O3 2.32, Y2O3 16.60, Sc2O3 1.57, Al2O3 3.06, B2O3 22.06, FeO 0.94, MnO 23.33, CaO 0.58, BeO 2.84, total 97.57 wt.%.The empirical formula based on 24 O apfu is (Y1.21REE0.78Th0.01)Σ2(Mn3.47Y0.34Ca0.11Fe2+0.08)Σ4(Al0.63Sc0.24Fe2+0.06□0.07)Σ1[(Si2.10B6.69Be1.20)Σ9.99O24], where REE = (Yb0.47Lu0.12Dy0.04Er0.07Tm0.03 Ho0.01Gd0.02Sm0.01Tb0.01)Σ0.78. Badakhshanite-(Y) is orthorhombic, space group Pnma, a 12.852(1), b 4.5848(5), c 12.8539(8) Å, V 757.38(7) Å3, Z = 2. The crystal structure was refined to R1 = 4.31% based on 1431 unique [F > 4σF] reflections. In the crystal structure of badakhshanite-(Y), a layer of tetrahedra parallel to (010) is composed of four different tetrahedrally coordinated sites: Si, B(1), B(2), and T (<Si–O> = 1.623 Å, <B(1)–O> = 1.485 Å, <B(2)–O> = 1.479 Å, <T–O> = 1.557 Å), which form four-, five-, and eight-membered rings, having the composition (Si2B7BeO24). Between the sheets of tetrahedra, there are three cation sites: M(1), M(2), and M(3) (<M(1)–O> = 2.346 Å, <M(2)–O> = 2.356 Å, <M(3)–O> = 2.016 Å) occupied by Y(REE), Mn2+(Y, Ca, Fe2+), and Al(Sc), respectively. The M(1,2) sites ideally give Y2Mn4apfu; the M(3) site ideally gives Al apfu. Badakhshanite-(Y) is an Al- and Be-analogue of perettiite-(Y).

The crystal structure of some chamosite minerals (With Plate XII)

1951 ◽  
Vol 29 (212) ◽  
pp. 502-525 ◽  
Author(s):  
G. W. Brindley ◽  
K. C. Dunham ◽  
V. A. Eyles ◽  
J. H. Taylor
Keyword(s):  
Crystal Structure ◽  
Close Association

Chamosite is a commonly occurring hydrous ferrous silicate frequently found in close association with chalybite in marine mudstone deposits, the composition of different beds ranging from almost pure chamosite to pure chalybite. In oolitic ironstones chamosite is found both in the ooliths themselves and also in the groundmass. It occurs as a constituent in shales, as a cementing mineral in sandstones, and is occasionally found in lateritic and other deposits. Mineralogically it is usually regarded as a chlorite, or akin to the chlorites, but evidence has been accumulating which tends to show that some varieties may not be chlorites at all, but are probably closely related to the kaolin group of minerals (Brindley, 1949).

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