Structures and ice-binding faces of the alanine-rich type I antifreeze proteinsThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Shruti N. Patel ◽  
Steffen P. Graether

Antifreeze proteins (AFPs) protect cold-blooded organisms from the damage caused by freezing through their ability to inhibit ice growth. The type I AFP family, found in several fish species, contains proteins that have a high alanine content (>60% of the sequence) and structures that are almost all α-helical. We examine the structure of the type I AFP isoforms HPLC6 from winter flounder, shorthorn sculpin 3, and the winter flounder hyperactive type I AFP. The HPLC6 isoform structure consists of a single α-helix that is 37 residues long, whereas the shorthorn sculpin 3 isoform consists of two helical regions separated by a kink. The high-resolution structure of the hyperactive type I AFP has yet to be determined, but circular dichroism data and analytical ultracentrifugation suggest that the 195 residue protein is a side-by-side dimer of two α-helices. The alanine-rich ice-binding faces of HPLC6 and hyperactive type I AFP are discussed, and we propose that the ice-binding face of the shorthorn sculpin 3 AFP contains Ala14, Ala19, and Ala25. We also propose that the denaturation of hyperactive type I AFP at room temperature is explained by the stabilization of the dimerization interface through hydrogen bonds.

2015 ◽  
Vol 17 (15) ◽  
pp. 9984-9990 ◽  
Author(s):  
S. Alireza Bagherzadeh ◽  
Saman Alavi ◽  
John A. Ripmeester ◽  
Peter Englezos

The winter flounder antifreeze protein (wf-AFP) acts as a gas hydrate crystal inhibitor by binding to the empty-half cages at the hydrate surfaceviathe cooperative action between methyl groups of threonine and alanine residues.


2021 ◽  
Vol 2021 (6) ◽  
Author(s):  
Henning Bahl ◽  
Tim Stefaniak ◽  
Jonas Wittbrodt

Abstract The presence of charged Higgs bosons is a generic prediction of multiplet extensions of the Standard Model (SM) Higgs sector. Focusing on the Two-Higgs-Doublet-Model (2HDM) with type I and lepton-specific Yukawa sectors, we discuss the charged Higgs boson collider phenomenology in the theoretically and experimentally viable parameter space. While almost all existing experimental searches at the LHC target the fermionic decays of charged Higgs bosons, we point out that the bosonic decay channels — especially the decay into a non-SM-like Higgs boson and a W boson — often dominate over the fermionic channels. Moreover, we revisit two genuine BSM effects on the properties of the discovered Higgs boson — the charged Higgs contribution to the diphoton rate and the Higgs decay to two light Higgs bosons — and their implication for the charged Higgs boson phenomenology. As main result of the present paper, we propose five two-dimensional benchmark scenarios with distinct phenomenological features in order to facilitate the design of dedicated LHC searches for charged Higgs bosons decaying into a W boson and a light, non-SM-like Higgs boson.


Nature ◽  
1995 ◽  
Vol 375 (6530) ◽  
pp. 427-431 ◽  
Author(s):  
F. Sicheri ◽  
D. S. C. Yang

Author(s):  
Oliver Gutiérrez-Hernández ◽  
Luis Ventura García

Multiplicity arises when data analysis involves multiple simultaneous inferences, increasing the chance of spurious findings. It is a widespread problem frequently ignored by researchers. In this paper, we perform an exploratory analysis of the Web of Science database for COVID-19 observational studies. We examined 100 top-cited COVID-19 peer-reviewed articles based on p-values, including up to 7100 simultaneous tests, with 50% including >34 tests, and 20% > 100 tests. We found that the larger the number of tests performed, the larger the number of significant results (r = 0.87, p < 10−6). The number of p-values in the abstracts was not related to the number of p-values in the papers. However, the highly significant results (p < 0.001) in the abstracts were strongly correlated (r = 0.61, p < 10−6) with the number of p < 0.001 significances in the papers. Furthermore, the abstracts included a higher proportion of significant results (0.91 vs. 0.50), and 80% reported only significant results. Only one reviewed paper addressed multiplicity-induced type I error inflation, pointing to potentially spurious results bypassing the peer-review process. We conclude the need to pay special attention to the increased chance of false discoveries in observational studies, including non-replicated striking discoveries with a potentially large social impact. We propose some easy-to-implement measures to assess and limit the effects of multiplicity.


Type I (a) diamonds contain high concentrations of nitrogen, almost all of which is in an aggregated form. The two main aggregates are recognized by characteristic absorption features in the infrared region of the spectrum. These are called A and B features; usually a peak designated B' is also present. When such diamonds were heated at 1960 °C and above under a stabilizing pressure of 85kbar (8.5 GPa) the nitrogen aggregates partially dissociated, producing single substitutional atoms which were identified by electron paramagnetic resonance (e.p.r.) measurements. Experiments with selected diamonds, showing wide variations in their characteristic infrared absorption, determined the relative stability of the A and B centres. Optical measurements led to the determination of a general relation between the strengths of the A, B and B' features. The experimental observations suggest a scheme for the occurrence of type I (a) diamonds containing nitrogen atoms which have aggregated into A centres; type I (b) diamonds can also be included in this scheme.


2020 ◽  
Vol 492 (3) ◽  
pp. 3073-3090 ◽  
Author(s):  
Eduardo A D Lacerda ◽  
Sebastián F Sánchez ◽  
R Cid Fernandes ◽  
Carlos López-Cobá ◽  
Carlos Espinosa-Ponce ◽  
...  

ABSTRACT We study the presence of optically-selected active galactic nuclei (AGNs) within a sample of 867 galaxies extracted from the extended Calar-Alto Legacy Integral Field spectroscopy Area (eCALIFA) spanning all morphological classes. We identify 10 Type-I and 24 Type-II AGNs, amounting to ∼4 per cent of our sample, similar to the fraction reported by previous explorations in the same redshift range. We compare the integrated properties of the ionized and molecular gas, and stellar population of AGN hosts and their non-active counterparts, combining them with morphological information. The AGN hosts are found in transitory parts (i.e. green-valley) in almost all analysed properties which present bimodal distributions (i.e. a region where reside star-forming galaxies and another with quiescent/retired ones). Regarding morphology, we find AGN hosts among the most massive galaxies, with enhanced central stellar-mass surface density in comparison to the average population at each morphological type. Moreover, their distribution peaks at the Sab-Sb classes and none are found among very late-type galaxies (&gt;Scd). Finally, we inspect how the AGN could act in their hosts regarding the quenching of star-formation. The main role of the AGN in the quenching process appears to be the removal (or heating) of molecular gas, rather than an additional suppression of the already observed decrease of the star-formation efficiency from late-to-early type galaxies.


2020 ◽  
Vol 21 (8) ◽  
pp. 2857
Author(s):  
Mahesh Chandra Patra ◽  
Maria Batool ◽  
Muhammad Haseeb ◽  
Sangdun Choi

Toll-like receptor 3 (TLR3) provides the host with antiviral defense by initiating an immune signaling cascade for the production of type I interferons. The X-ray structures of isolated TLR3 ectodomain (ECD) and transmembrane (TM) domains have been reported; however, the structure of a membrane-solvated, full-length receptor remains elusive. We investigated an all-residue TLR3 model embedded inside a phospholipid bilayer using molecular dynamics simulations. The TLR3-ECD exhibited a ~30°–35° tilt on the membrane due to the electrostatic interaction between the N-terminal subdomain and phospholipid headgroups. Although the movement of dsRNA did not affect the dimer integrity of TLR3, its sugar-phosphate backbone was slightly distorted with the orientation of the ECD. TM helices exhibited a noticeable tilt and curvature but maintained a consistent crossing angle, avoiding the hydrophobic mismatch with the bilayer. Residues from the αD helix and the CD and DE loops of the Toll/interleukin-1 receptor (TIR) domains were partially absorbed into the lower leaflet of the bilayer. We found that the previously unknown TLR3-TIR dimerization interface could be stabilized by the reciprocal contact between αC and αD helices of one subunit and the αC helix and the BB loop of the other. Overall, the present study can be helpful to understand the signaling-competent form of TLR3 in physiological environments.


1986 ◽  
Vol 64 (3) ◽  
pp. 578-582 ◽  
Author(s):  
Ming H. Kao ◽  
Garth L. Fletcher ◽  
Nam C. Wang ◽  
Choy L. Hew

Previous studies have established that the capacity of the glycopeptide antifreezes to depress the freezing temperature of aqueous solutions is positively correlated with molecular weight. The present study was carried out to determine whether a similar correlation existed within the antifreeze peptides. Two approaches were used. Initially, the antifreeze activity (thermal hysteresis) curves of antifreeze peptides from winter flounder, Pseudopleuronectes americanus (molecular weight, 3300), shorthorn sculpin, Myoxocephalus scorpius (molecular weight, 4000), ocean pout, Macrozoarces americanus (molecular weight, 6000), and sea raven, Hemitripterus americanus (molecular weight, 9700), were compared. In the second approach, a more specific comparison was made of two different sized antifreeze peptide components (molecular weights, 2900 and 4000) from the shorthorn sculpin. In both approaches, antifreeze peptide activity was positively correlated with molecular weight and the curve illustrating this relationship suggests that any reduction in molecular weight below 3300 will result in a disproportionate decline in activity. The relatively small antifreeze peptides from the winter flounder and shorthorn sculpin had greater activity than did glycopeptide antifreezes of similar size. However, glycopeptide antifreezes with a molecular weight of 10 000 or more had activities that exceeded that of any known antifreeze peptide. Increases in molecular weight of antifreeze peptides above 4000 resulted in a decline in antifreeze activity per milligram protein. Therefore, in terms of ability to depress the freezing temperature, there appears to be no advantage in evolving large antifreeze peptide molecules.


2005 ◽  
Vol 79 (21) ◽  
pp. 13317-13325 ◽  
Author(s):  
Hong Liu ◽  
Walter F. Stafford ◽  
Marlene Bouvier

ABSTRACT E3-19K is a type I membrane glycoprotein expressed by adenoviruses (Ads) to modulate host antiviral immune responses. We have developed an expression system for the endoplasmic reticulum lumenal domain (residues 1 to 100) of Ad type 2 E3-19K tagged with a C-terminal His6 sequence in baculovirus-infected insect cells. In this system, recombinant E3-19K is secreted into the culture medium. A characterization of soluble E3-19K by analytical ultracentrifugation and circular dichroism showed that the protein is monomeric and adopts a stable and correctly folded tertiary structure. Using a gel mobility shift assay and analytical ultracentrifugation, we showed that soluble E3-19K associates with soluble peptide-filled and peptide-deficient HLA-A*1101 molecules. This is the first example of a viral immunomodulatory protein that interacts with conformationally distinct forms of class I major histocompatibility complex molecules. The E3-19K/HLA-A*1101 complexes formed in a 1:1 stoichiometry with equilibrium dissociation constants (Kd ) of 50 ± 10 nM for peptide-filled molecules and of about 10 μM for peptide-deficient molecules. A temperature-dependent proteolysis study revealed that the association of E3-19K with peptide-deficient HLA-A*1101 molecules stabilizes the binding groove. Importantly, our studies showed that peptide-deficient HLA-A*1101 molecules sequestered by E3-19K are capable of binding antigenic peptides and maturing into peptide-filled molecules. This firmly establishes that E3-19K does not block binding of antigenic peptides. Together, our results suggest that Ads have evolved to exploit the late and early stages of the class I antigen presentation pathway.


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