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1.
Revisiting sORFs: overcoming challenges to identify and characterize functional microproteins.
Schlesinger, D, Elsässer, SJ
The FEBS journal. 2022;(1):53-74
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Abstract
Short ORFs (sORFs), that is, occurrences of a start and stop codon within 100 codons or less, can be found in organisms of all domains of life, outnumbering annotated protein-coding ORFs by orders of magnitude. Even though functional proteins smaller than 100 amino acids are known, the coding potential of sORFs has often been overlooked, as it is not trivial to predict and test for functionality within the large number of sORFs. Recent advances in ribosome profiling and mass spectrometry approaches, together with refined bioinformatic predictions, have enabled a huge leap forward in this field and identified thousands of likely coding sORFs. A relatively low number of small proteins or microproteins produced from these sORFs have been characterized so far on the molecular, structural, and/or mechanistic level. These however display versatile and, in some cases, essential cellular functions, allowing for the exciting possibility that many more, previously unknown small proteins might be encoded in the genome, waiting to be discovered. This review will give an overview of the steadily growing microprotein field, focusing on eukaryotic small proteins. We will discuss emerging themes in the molecular action of microproteins, as well as advances and challenges in microprotein identification and characterization.
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2.
Galvanization of Protein-Protein Interactions in a Dynamic Zinc Interactome.
Kocyła, A, Tran, JB, Krężel, A
Trends in biochemical sciences. 2021;(1):64-79
Abstract
The presence of Zn2+ at protein-protein interfaces modulates complex function, stability, and introduces structural flexibility/complexity, chemical selectivity, and reversibility driven in a Zn2+-dependent manner. Recent studies have demonstrated that dynamically changing Zn2+ affects numerous cellular processes, including protein-protein communication and protein complex assembly. How Zn2+-involved protein-protein interactions (ZPPIs) are formed and dissociate and how their stability and reactivity are driven in a zinc interactome remain poorly understood, mostly due to experimental obstacles. Here, we review recent research advances on the role of Zn2+ in the formation of interprotein sites, their architecture, function, and stability. Moreover, we underline the importance of zinc networks in intersystemic communication and highlight bioinformatic and experimental challenges required for the identification and investigation of ZPPIs.
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3.
Ultrafast Fluorescence Spectroscopy via Upconversion and Its Applications in Biophysics.
Cao, S, Li, H, Zhao, Z, Zhang, S, Chen, J, Xu, J, Knutson, JR, Brand, L
Molecules (Basel, Switzerland). 2021;(1)
Abstract
In this review, the experimental set-up and functional characteristics of single-wavelength and broad-band femtosecond upconversion spectrophotofluorometers developed in our laboratory are described. We discuss applications of this technique to biophysical problems, such as ultrafast fluorescence quenching and solvation dynamics of tryptophan, peptides, proteins, reduced nicotinamide adenine dinucleotide (NADH), and nucleic acids. In the tryptophan dynamics field, especially for proteins, two types of solvation dynamics on different time scales have been well explored: ~1 ps for bulk water, and tens of picoseconds for "biological water", a term that combines effects of water and macromolecule dynamics. In addition, some proteins also show quasi-static self-quenching (QSSQ) phenomena. Interestingly, in our more recent work, we also find that similar mixtures of quenching and solvation dynamics occur for the metabolic cofactor NADH. In this review, we add a brief overview of the emerging development of fluorescent RNA aptamers and their potential application to live cell imaging, while noting how ultrafast measurement may speed their optimization.
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4.
Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations.
Thakral, S, Sonje, J, Munjal, B, Suryanarayanan, R
Advanced drug delivery reviews. 2021;:1-19
Abstract
This review aims to provide an overview of the current knowledge on protein stabilization during freezing and freeze-drying in relation to stress conditions commonly encountered during these processes. The traditional as well as refined mechanisms by which excipients may stabilize proteins are presented. These stabilizers encompass a wide variety of compounds including sugars, sugar alcohols, amino acids, surfactants, buffers and polymers. The rational selection of excipients for use in frozen and freeze-dried protein formulations is presented. Lyophilized protein formulations are generally multicomponent systems, providing numerous possibilities of excipient-excipient and protein-excipient interactions. The interplay of different formulation components on the protein stability and excipient functionality in the frozen and freeze-dried systems are reviewed, with discussion of representative examples of such interactions.
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5.
Initiation and Prevention of Biological Damage by Radiation-Generated Protein Radicals.
Gebicki, JM, Nauser, T
International journal of molecular sciences. 2021;(1)
Abstract
Ionizing radiations cause chemical damage to proteins. In aerobic aqueous solutions, the damage is commonly mediated by the hydroxyl free radicals generated from water, resulting in formation of protein radicals. Protein damage is especially significant in biological systems, because proteins are the most abundant targets of the radiation-generated radicals, the hydroxyl radical-protein reaction is fast, and the damage usually results in loss of their biological function. Under physiological conditions, proteins are initially oxidized to carbon-centered radicals, which can propagate the damage to other molecules. The most effective endogenous antioxidants, ascorbate, GSH, and urate, are unable to prevent all of the damage under the common condition of oxidative stress. In a promising development, recent work demonstrates the potential of polyphenols, their metabolites, and other aromatic compounds to repair protein radicals by the fast formation of less damaging radical adducts, thus potentially preventing the formation of a cascade of new reactive species.
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Cyclodextrins based delivery systems for macro biomolecules.
Liu, J, Ding, X, Fu, Y, Xiang, C, Yuan, Y, Zhang, Y, Yu, P
European journal of medicinal chemistry. 2021;:113105
Abstract
Macro biomolecules are of vital importance in regulating the biofunctions in organisms, in which proteins (including peptides when mentioned below) and nucleic acids (NAs) are the most important. Therefore, these proteins and NAs can be applied as "drugs" to regulate the biofunctions from abnormal to normal. Either for proteins and NAs, the most challenging thing is to avoid the biodegradation or physicochemical degradation before they reach the targeted location, and then functions as complete functional structures. Hence, appropriate delivery systems are very important which can protect them from these degradations. Cyclodextrins (CDs) based delivery systems achieved mega successes due to their outstanding pharmaceutical properties and there have been several reviews on CDs based small molecule drug delivery systems recently. But for biomolecules, which are getting more and more important for modern therapies, however, there are very few reviews to systematically summarize and analyze the CDs-based macro biomolecules delivery systems, especially for proteins. In this review, there were some of the notable examples were summarized for the macro biomolecules (proteins and NAs) delivery based on CDs. For proteins, this review included insulin, lysozyme, bovine serum albumin (BSA), green fluorescent protein (GFP) and IgG's, etc. deliveries in slow release, stimulating responsive release or targeting release manners. For NAs, this review summarized cationic CD-polymers and CD-cluster monomers as NAs carriers, notably, including the multicomponents targeting CD-based carriers and the virus-like RNA assembly method siRNA carriers.
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7.
Site-Selective, Chemical Modification of Protein at Aromatic Side Chain and Their Emergent Applications.
Chowdhury, A, Chatterjee, S, Pongen, A, Sarania, D, Tripathi, NM, Bandyopadhyay, A
Protein and peptide letters. 2021;(7):788-808
Abstract
Site-selective chemical modification of protein side chain has probed enormous opportunities in the fundamental understanding of cellular biology and therapeutic applications. Primarily, in the field of biopharmaceuticals, the formulation of bioconjugates has been found to have more potential than an individual constituent. In this regard, Lysine and Cysteine are the most widely used endogenous amino acid for these purposes. Recently, the aromatic side chain residues (Trp, Tyr, and His) that are low abundant in protein have gained more attention in therapeutic applications due to their advantages of chemical reactivity and specificity. This review discusses the site-selective bioconjugation methods for aromatic side chains (Trp, Tyr and His) and highlights the developed strategies in the last three years, along with their applications. Also, the review highlights the prevalent methods published earlier. We have examined that metal-catalyzed and photocatalytic reactions are gaining more attention for bioconjugation, though their practical operation is under development. The review has been summarized with the future perspective of protein and peptide conjugations contemplating therapeutic applications and challenges.
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8.
Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules.
Smethurst, DGJ, Shcherbik, N
The Journal of biological chemistry. 2021;(6):101374
Abstract
Metal ions provide considerable functionality across biological systems, and their utilization within biomolecules has adapted through changes in the chemical environment to maintain the activity they facilitate. While ancient earth's atmosphere was rich in iron and manganese and low in oxygen, periods of atmospheric oxygenation significantly altered the availability of certain metal ions, resulting in ion replacement within biomolecules. This adaptation mechanism has given rise to the phenomenon of metal cofactor interchangeability, whereby contemporary proteins and nucleic acids interact with multiple metal ions interchangeably, with different coordinated metals influencing biological activity, stability, and toxic potential. The ability of extant organisms to adapt to fluctuating metal availability remains relevant in a number of crucial biomolecules, including the superoxide dismutases of the antioxidant defense systems and ribonucleotide reductases. These well-studied and ancient enzymes illustrate the potential for metal interchangeability and adaptive utilization. More recently, the ribosome has also been demonstrated to exhibit interchangeable interactions with metal ions with impacts on function, stability, and stress adaptation. Using these and other examples, here we review the biological significance of interchangeable metal ions from a new angle that combines both biochemical and evolutionary viewpoints. The geochemical pressures and chemical properties that underlie biological metal utilization are discussed in the context of their impact on modern disease states and treatments.
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9.
Protein Microarrays for Ocular Diseases.
Solís-Fernández, G, Montero-Calle, A, Alonso-Navarro, M, Fernandez-Torres, MÁ, Lledó, VE, Garranzo-Asensio, M, Barderas, R, Guzman-Aranguez, A
Methods in molecular biology (Clifton, N.J.). 2021;:239-265
Abstract
The eye is a multifaceted organ organized in several compartments with particular properties that reflect their diverse functions. The prevalence of ocular diseases is increasing, mainly because of its relationship with aging and of generalized lifestyle changes. However, the pathogenic molecular mechanisms of many common eye pathologies remain poorly understood. Considering the unquestionable importance of proteins in cellular processes and disease progression, proteomic techniques, such as protein microarrays, represent a valuable approach to analyze pathophysiological protein changes in the ocular environment. This technology enables to perform multiplex high-throughput protein expression profiling with minimal sample volume requirements broadening our knowledge of ocular proteome network in eye diseases.In this review, we present a brief summary of the main types of protein microarrays (antibody microarrays, reverse-phase protein microarrays, and protein microarrays) and their application for protein change detection in chronic ocular diseases such as dry eye, age-related macular degeneration, diabetic retinopathy, and glaucoma. The validation of these specific protein changes in eye pathologies may lead to the identification of new biomarkers, depiction of ocular disease pathways, and assistance in the diagnosis, prognosis, and development of new therapeutic options for eye pathologies.
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10.
Functional biomedical materials derived from proteins in the acquired salivary pellicle.
Zhang, F, Cheng, Z, Ding, C, Li, J
Journal of materials chemistry. B. 2021;(33):6507-6520
Abstract
In the oral environment, the acquired salivary pellicle (ASP) on the tooth surface comprises proteins, glycoproteins, carbohydrates, and lipids. The ASP can specifically and rapidly adsorb on the enamel surface to provide effective lubrication, protection, hydration, and remineralisation, as well as be recognised by various bacteria to form a microbial biofilm (plaque). The involved proteins, particularly various phosphoproteins such as statherins, histatins, and proline-rich proteins, are vital to their specific functions. This review first describes the relationship between the biological functions of these proteins and their structures. Subsequently, recent advances in functional biomedical materials derived from these proteins are reviewed in terms of dental/bone therapeutic materials, antibacterial materials, tissue engineering materials, and coatings for medical devices. Finally, perspectives and challenges regarding the rational design and biomedical applications of ASP-derived materials are discussed.