The bacterial macrolide rapamycin is an efficacious anticancer agent against solid tumors. In a hypoxic environment, the increase in mass of tumors dependent on recruitment mitogens and nutrients. When nutrient concentrations change, particularly those essential amino acids, mammalian Target Rapamycin (mTOR) functions regulatory pathways that control ribosome biogenesis cell growth. bacteria, independently regulated by acids adenosine triphosphate (ATP). Here we demonstrate mTOR pathway...

Activation of the protein p70 s6k by mitogens leads to increased translation a family messenger RNAs that encode essential components synthetic apparatus. kinase requires hierarchical phosphorylation at multiple sites, culminating in threonine position 229 (Thr ), catalytic domain. The homologous site B (PKB), Thr 308 , has been shown be phosphorylated phosphoinositide-dependent PDK1. A regulatory link between and PKB was demonstrated, as PDK1 found selectively phosphorylate . More...

Mimicking the designs found in proteins Natural combine a range of useful features, including chemical diversity, ability to rapidly switch between preprogrammed shapes, and hierarchy structures. Panganiban et al. designed random copolymers with polar nonpolar groups, using many features (see Perspective by Alexander-Katz Van Lehn). Their structures could serve as “broad spectrum” surfactants, able promote solubilization organic solvents help preserve functionality aqueous environments....

AlphaFold 2 (AF2) has placed Molecular Biology in a new era where we can visualize, analyze and interpret the structures functions of all proteins solely from their primary sequences. We performed AF2 structure predictions for various protein systems, including globular proteins, multi-domain protein, an intrinsically disordered (IDP), randomized two larger (> 1000 AA), heterodimer homodimer complex. Our results show that along with three dimensional (3D) structures, also decodes sequences...

Mitogen-induced activation of p70(s6k) is associated with the phosphorylation specific sites which are negatively affected by immunosuppressant rapamycin, fungal metabolite wortmannin, and methylxanthine SQ20006. Recent reports have focused on role amino terminus p85(s6k) isoform in mediating kinase activity, observation that amino-terminal truncation mutants activated presence rapamycin while retaining their sensitivity to wortmannin. Here we show effects previously described amino-...

Employing specific inhibitors and docking-site mutants of growth factor receptors, recent studies have indicated that the insulin-induced increase in 40S ribosomal protein S6 initiation 4E binding 1 (4E-BP1) phosphorylation is mediated by mTOR/FRAP-p70s6k signal transduction pathway. However, it has not been resolved whether both proteins p70s6k or they reside on parallel pathways which bifurcate upstream p70s6k. Here we used either rapamycin-resistant, kinase-dead, wild-type variants to...

A critical step in S6 kinase 1 (S6K1) activation is Thr²²⁹ phosphorylation the loop by phosphoinositide-dependent protein (PDK1). requires prior of Ser/Thr-Pro sites autoinhibitory domain and Thr³⁸⁹ linker domain, consistent with PDK1 more effectively catalyzing a variant harboring acidic residues these positions (S6K1-E389D₃E). S6K1-E389D₃E has high basal activity exhibits partial resistance to rapamycin wortmannin, its can be further augmented...

Activation of p70s6k in cells stimulated with serum correlates the phosphorylation seven sites. Pretreatment Swiss 3T3 immunosuppressant rapamycin blocks four these sites (Thr229, Thr389, Ser404, and Ser411), whereas proceeds remaining three (Ser418, Thr421, Ser424). If is added post-serum stimulation, pattern qualitatively similar except that Ser411 still highly phosphorylated. The inhibitory effect on serum-induced activation Thr229, rescued by FK506, providing further evidence exerted...

Abstract Throughout nature, elegant biophotonic structures have evolved into sophisticated arrangements of pigments and structural reflectors that manipulate light in the skin, cuticles, feathers fur animals. Not many spherical are known those described often angle dependent or spectrally tuned. White scattering by flexible skin cuttlefish ( Sepia officinalis ) is examined how unique structure composition leucophore cells serve as physiologically passive approximating optical properties a...

Adaptive reflective surfaces have been a challenge for both electronic paper (e-paper) and biological organisms. Multiple colours, contrast, polarization, reflectance, diffusivity texture must all be controlled simultaneously without optical losses in order to fully replicate the appearance of natural vividly communicate information. This review merges frontiers knowledge adaptive coloration, with focus on cephalopods, synthetic e-paper within consistent framework scientific metrics....

The activation of p70s6k is associated with multiple phosphorylations at two sets sites. first set, S411, S418, T421, and S424, reside within the autoinhibitory domain, each contains a hydrophobic residue -2 proline +1. second set sites, T229 (in catalytic domain) T389 S404 linker region), are rapamycin sensitive flanked by bulky aromatic residues. Here we describe identification mutational analysis three new phosphorylation T367, S371, T447, all which have recognition motif similar to that...

Abstract Reflectins are a unique group of structural proteins involved in dynamic optical systems cephalopods that modulate incident light or bioluminescence. We describe cloning, characterization, and properties reflectin‐based domain, refCBA, from reflectin 1a Hawaiian bobtail squid, Euprymna scolopes . Thin films created the recombinant protein refCBA display interesting features when is appropriately organized. RefCBA was cloned expressed as soluble enabling purification, with little...

We use AlphaFold2 (AF2) to model the monomer and dimer structures of an intrinsically disordered protein (IDP), Nvjp-1 , assisted by molecular dynamics (MD) simulations. observe relatively rigid dimeric when compared with structures. suggest that conformations from multiple AF2 models those MD trajectories exhibit a coherent trend: IDP are deviated each other well-folded consistent other. residue-residue interaction network (RIN) derived contact map which show interactions in mainly...

The S6/H4 kinase purified from human placenta catalyzes phosphorylation of the S6 ribosomal protein, histone H4, and myelin basic protein. In vitro activation p60 requires removal an autoinhibitory domain by mild trypsin digestion autophosphorylation catalytic (p40 kinase). two autophosphorylation/autoactivation sites contain sequences SSMVGTPY (site 1) SVIDPVPAPVGDSHVDGAAK 2). These identify as rac-activated PAK65 (Martin, G. A., Bollag, G., McCormick, F. Abo, A.(1995) EMBO J. 14,...

Organophosphates are some of the most acutely toxic compounds synthesized on an industrial scale, and organophosphorus hydrolase (OPH) has ability to hydrolyze inactivate a number these chemicals. However, OPH activity is vulnerable harsh environmental conditions that would accompany its practical utility in field; limitation can also be extended required for incorporation into useful materials. Here we present evidence entrapment silk fibroin leads stabilization under variety otherwise...

Regenerated silk fibroin, a biopolymer derived from silkworm cocoons, is versatile material that has been widely explored for number of applications (e.g., drug delivery, tissue repair, biocompatible electronics substrates, and optics) due to its attractive biochemical properties processability. Here, we report on the free-form printing silk-based, 3D microstructures through multiphoton lithography. Utilizing lithography in conjunction with specific photoinitiator chemistry postprint...

Abstract The controlled binding of proteins on nanoparticle surfaces remains a grand challenge required for many applications ranging from biomedical to energy storage. difficulty in achieving this ability arises the different functional groups biomolecule that can adsorb surface. While most only adopt single structure, metamorphic access at least two conformations, which presents intriguing opportunities exploit such structural variations nanoparticles. Such effects are examined using...

Abstract AlphaFold 2 (AF2) has placed Molecular Biology in a new era where we can visualize, analyze and interpret the structures functions of all proteins solely from their primary sequences. We performed AF2 structure predictions for various protein systems, including globular proteins, multi-domain protein, an intrinsically disordered (IDP), randomized two larger (> 1000 AA), heterodimer homodimer complex. Our results show that along with three dimensional (3D) structures, also decodes...

Abstract Despite the success of AlphaFold2 (AF2), it is unclear how AF2 models accommodate for ligand binding. Here, we start with a protein sequence from Acidimicrobiaceae TMED77 (T7RdhA) potential catalyzing degradation per- and polyfluoroalkyl substances (PFASs). experiments identified T7RdhA as corrinoid iron-sulfur (CoFeSP) which uses norpseudo-cobalamin (BVQ) cofactor two Fe 4 S clusters catalysis. Docking molecular dynamics simulations suggest that perfluorooctanoic acetate (PFOA)...