Mre11-Rad50 oligomerization promotes DNA double-strand break repair

The conserved Mre11-Rad50 (MR) complex is crucial for the detection, signaling, end tethering and processing of DNA double-strand breaks (DSBs). While it was known for decades that MR foci formation at DSBs accompanies repair, the underlying molecular assembly mechanisms and functional implications remained unclear. Combining pathway reconstitution in electron microscopy, biochemical assays and genetic studies, we show that S. cerevisiae MR oligomerizes via a conserved Rad50 beta-sheet to higher-order assemblies, which bind DNA with positive cooperativity. We designed Rad50 point mutants with enhanced or disrupted MR oligomerization, and demonstrate that MR oligomerization facilitates foci formation, DNA damage signaling and repair in vivo. MR oligomerization does not affect its exonuclease activity but drives endonucleolytic cleavage at multiple sites on the 5'-terminated DNA strand near DSBs. Interestingly, mutations in the human Rad50 beta-sheet are linked to hereditary cancer predisposition and our findings might provide new insights into their potential role in chemoresistance.

Protein world and hemochiralty

Protein world hypothesis and the origin of homochiralty are described. By using enzyme catalyzing itself, L-amino acid can replicate. L-amino acid also catalyze D-sugar production. By using Ramachandran plot, L-amino acid is favored for generating right alpha helix and beta sheet. Thus, homochiralty of earth happened.

Investigating the conformational dynamics of SARS-CoV-2 NSP6 protein with emphasis on non-transmembrane 91-112 & 231-290 regions

The NSP6 protein of SARS-CoV-2 is a transmembrane protein, with some regions lying outside the membrane. Besides, a brief role of NSP6 in autophagosome formation, this is not studied significantly. Also, there is no structural information available till date. Based on the prediction by TMHMM server for transmembrane prediction, it is found that the N-terminal residues (1-11), middle region residues (91-112) and C-terminal residues (231-290) lies outside the membrane. Molecular Dynamics (MD) simulations showed that NSP6 consisting of helical structures, whereas membrane outside lying region (91-112) showed partial helicity, which further used as model and obtain disordered type conformation after 1.5 microseconds. Whereas, the residues 231-290 has both helical and beta sheet conformations in its structure model. A 200ns simulations resulted in the loss of beta sheet structures, while helical regions remained intact. Further, we have characterized the residue 91-112 by using reductionist approaches. The NSP6 (91-112) was found disordered like in isolation, which gain helical conformation in different biological mimic environmental conditions. These studies can be helpful to study NSP6 (91-112) interactions with host proteins, where different protein conformation might play significant role. The present study adds up more information about NSP6 protein aspect, which could be exploited for its host protein interaction and pathogenesis.

Structure and Stability of the designer protein WRAP-T and its permutants

β-propeller proteins are common natural disc-like pseudo-symmetric proteins that contain multiple repeats ('blades') each consisting of a 4-stranded anti-parallel beta-sheet. So far, 4- to 12-bladed β-propellers have been discovered in nature showing large functional and sequential variation. Using computational design approaches, we created perfectly symmetric β-propellers out of natural pseudo-symmetric templates. These proteins are useful tools to study protein evolution of this very diverse fold. While the 7-bladed architecture is the most common, no symmetric 7-bladed monomer has been created and characterized so far. Here we describe such a engineered protein, based on a highly symmetric natural template, and test the effects of circular permutation on its stability. Geometrical analysis of this protein and other artificial symmetrical proteins reveals no systematic constraint that could be used to help in engineering of this fold, and suggests sequence constraints unique to each β-propeller sub-family.

ANALISIS IN SILICO PROTEIN CLOCK (CIRCADIAN LOCOMOTOR OUTPUT CYCLES KAPUT) PADA Patagioenas fasciata monilis

CLOCK merupakan protein penting yang berperan dalam adaptasi ekologi dan fisiologi dibanyak organisme. Studi sebelumnya menjelaskan bahwa CLOCK memiliki pengaruh terhadap perubahan perilaku hewan. Penelitian ini bertujuan untuk menganalisis protein CLOCK pada burung Patagioenas fasciata monilis secara in silico. Metode yang digunakan pada penelitian ini adalah metode homologi. Hasil struktur model berdasarkan assessment menunjukkan akurasi model yang mendekati struktur sebenarnya. Struktur model yang diperoleh memiliki berat 96200,04 Daltons, tiga daerah struktur beta-sheet, lima daerah struktur alpha-helix, 1,47 % daerah otuliers, dua residu C-Beta Deviations, nilai identity 94,43 %, 34 sudut buruk, nilai QMEAN -1,69 dan nilai GMQE 0,31.

Destabilization potential of beta sheet breaker peptides on Abeta fibril structure: an insight from molecular dynamics simulation study

Destabilzation of Abeta protofibril by Beta Sheet Breaker (BSB) peptides.

Chemical Catalyst-Promoted Photooxygenation of Amyloid Proteins

Misfolded proteins produce aberrant fibrillar aggregates, called amyloid, that contain cross-beta-sheet higher order structures. The species generated in the aggregation processes (i.e., oligomers, protofibrils, and fibrils) are cytotoxic and can...