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Background: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive. Methods: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues. Results: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM. Conclusion: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications. [ABSTRACT FROM AUTHOR]

C17H13ClN2O2, monoclinic, P21/c (no. 14), a = 5.3601(4) Å, b = 10.6233(7) Å, c = 25.2125(16) Å, β = 92.920(5)°, V = 1433.96(17) Å3, Z = 4, Rgt(F) = 0.0495, wRref (F2) = 0.1143, T = 173(10) K. [ABSTRACT FROM AUTHOR]

The development of powerful and general methods to acquire ubiquitin (Ub) chains has prompted the deciphering of Ub‐mediated processes. Herein, the cysteine‐aminoethylation assisted chemical ubiquitination (CAACU) strategy is extended and improved to enable the efficient semi‐synthesis of atypical Ub chain analogues and Ub‐based probes. Combining the Cys aminoethylation and the auxiliary‐mediated protein ligation, several linkage‐ and length‐defined atypical Ub chains including di‐Ubs, K27C‐linked tri‐Ub, K11/K48C‐branched tri‐Ub, and even the SUMOlated Ub are successfully prepared from recombinantly expressed starting materials at about a 9–20 mg L−1 expression level. In addition, the utility of this strategy is demonstrated with the synthesis of a novel non‐hydrolyzable di‐Ub PA probe, which may provide a new useful tool for the mechanistic studies of deubiquitinase (DUB) recognition. [ABSTRACT FROM AUTHOR]

Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure. [ABSTRACT FROM AUTHOR]

Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies. [ABSTRACT FROM AUTHOR]

Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process. [ABSTRACT FROM AUTHOR]