The critical role of the variable domain in driving proteotoxicity and aggregation in full-length light chains.

Light chain (AL) amyloidosis is the most common systemic amyloid disease characterized by abnormal accumulation of amyloid fibrils derived from immunoglobulin light chains (LCs). Both full-length (FL) LCs and their isolated variable (VL) and constant (CL) domains contribute to amyloid deposits in multiple organs, with the VL domain predominantly forming the fibril core. However, the role and interplay of these domains in amyloid aggregation and toxicity are poorly understood.

Tying a true topological protein knot by cyclization.

Knotted proteins are fascinating to biophysicists because of their robust ability to fold into intricately defined three-dimensional structures with complex and topologically knotted arrangements. Exploring the biophysical properties of the knotted proteins is of significant interest, as they could offer enhanced chemical, thermal, and mechanostabilities. A true mathematical knot requires a closed path; in contrast, knotted protein structures have open N- and C-termini.

Structural insights into the regulation, ligand recognition, and oligomerization of bacterial STING.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling pathway plays a critical protective role against viral infections. Metazoan STING undergoes multilayers of regulation to ensure specific signal transduction. However, the mechanisms underlying the regulation of bacterial STING remain unclear.

Structure, dynamics, and stability of the smallest and most complex 7 protein knot.

Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 7 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus.

A High-Throughput Interbacterial Competition Screen Identifies ClpAP in Enhancing Recipient Susceptibility to Type VI Secretion System-Mediated Attack by .

The type VI secretion system (T6SS) is an effector delivery system used by Gram-negative bacteria to kill other bacteria or eukaryotic hosts to gain fitness. The plant pathogen utilizes its T6SS to kill other bacteria, such as . We observed that the T6SS-dependent killing outcome differs when using different T6SS-lacking, K-12 strains as a recipient cell.

Protein knots provide mechano-resilience to an AAA+ protease-mediated proteolysis with profound ATP energy expenses.

Knotted proteins are some of the most fascinating examples of how linear polypeptide chains can achieve intricate topological arrangements efficiently and spontaneously. The entanglements of polypeptide chains could potentially enhance their folding stabilities. We recently reported the unprecedented mechanostability of the Gordian (5) knotted family of human ubiquitin C-terminal hydrolases (UCHs) in the context of withstanding the mechanical unfolding of the bacterial AAA+ proteasome, ClpXP; a green fluorescence protein (GFP) was fused to the N-terminus of various UCHs as a reporter of the unfolding and degradation of these topologically knotted substrates, but it also limited the ability to examine the effect of untying the knotted topology via N-terminal truncation.

Comparative folding analyses of unknotted versus trefoil-knotted ornithine transcarbamylases suggest stabilizing effects of protein knots.

Ornithine transcarbamylases (OTCs) are conserved enzymes involved in arginine biosynthesis in microbes and the urea cycle in mammals. Recent bioinformatics analyses identified two unique OTC variants, N-succinyl-l-ornithine transcarbamylase from Bacteroides fragilis (BfSOTC) and N-acetyl-l-ornithine transcarbamylase from Xanthomonas campestris (XcAOTC). These two variants diverged from other OTCs during evolution despite sharing the common tertiary and quaternary structures, with the exception that the substrate recognition motifs are topologically knotted.

Topologically knotted deubiquitinases exhibit unprecedented mechanostability to withstand the proteolysis by an AAA+ protease.

More than one thousand knotted protein structures have been identified so far, but the functional roles of these knots remain elusive. It has been postulated that backbone entanglement may provide additional mechanostability. Here, we employed a bacterial proteasome, ClpXP, to mechanically unfold 5-knotted human ubiquitin C-terminal hydrolase (UCH) paralogs from their C-termini, followed by processive translocation into the proteolytic chamber for degradation.

Proximate, mineral composition and antioxidant activity of traditional small millets cultivated and consumed in Rayalaseema region of south India.

Background: Millets are a diverse group of small seeded grasses, widely grown around the world as cereal foods. This communication details the proximate, mineral profile and antioxidant activity of six different small millets (Finger, Foxtail, Proso, Little, Barnyard and Kodo millets) and their 21 cultivars that are traditionally cultivated and consumed in the region of Ralayaseema, south India.

Results: The proximate analysis revealed that these millets are rich in protein, fat, ash (mineral), total dietary fibre and total phenols with appreciable antioxidant activity.