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Advances in Protein Chemistry and Structural Biology

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https://read.qxmd.com/read/31036300/nucleobindins-and-encoded-peptides-from-cell-signaling-to-physiology
#1
Adelaine Kwun-Wai Leung, Naresh Ramesh, Christine Vogel, Suraj Unniappan
Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two NUCBs, nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2), were discovered during the 1990s. These two peptides are shown to have diverse functions, including the regulation of inflammation and bone formation, among others. In 2006, Oh-I and colleagues discovered that three peptides encoded within the NUCB2 could be processed by prohormone convertases. These peptides were named nesfatin-1, 2 and 3, mainly due to the satiety and fat influencing properties of nesfatin-1...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036299/from-traveler-to-homebody-which-signaling-mechanisms-sponge-larvae-use-to-become-adult-sponges
#2
Ilya Borisenko, Olga I Podgornaya, Alexander V Ereskovsky
Cell-to-cell signaling is responsible for regulation of many developmental processes such as proliferation, cell migration, survival, cell fate specification and axis patterning. In this article we discussed the role of signaling in the metamorphosis of sponges with a focus on epithelial-mesenchymal transition (EMT) accompanying this event. Sponges (Porifera) are an ancient lineage of morphologically simple animals occupying a basal position on the tree of life. The study of these animals is necessary for understanding the origin of multicellularity and the evolution of developmental processes...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036298/recent-advances-in-computational-studies-of-gpcr-g-protein-interactions
#3
Jinan Wang, Yinglong Miao
Protein-protein interactions are key in cellular signaling. G protein-coupled receptors (GPCRs), the largest superfamily of human membrane proteins, are able to transduce extracellular signals (e.g., hormones and neurotransmitters) to intracellular proteins, in particular the G proteins. Since GPCRs serve as primary targets of ~1/3 of currently marketed drugs, it is important to understand mechanisms of GPCR signaling in order to design selective and potent drug molecules. This chapter focuses on recent advances in computational studies of the GPCR-G protein interactions using bioinformatics, protein-protein docking and molecular dynamics simulation approaches...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036297/dopamine-signaling-in-the-striatum
#4
Emmanuel Valjent, Anne Biever, Giuseppe Gangarossa, Emma Puighermanal
The striatum integrates dopamine-mediated reward signals to generate appropriate behavior in response to glutamate-mediated sensory cues. Such associative learning relies on enduring neural plasticity in striatal GABAergic spiny projection neurons which, when altered, can lead to the development of a wide variety of pathological states. Considerable progress has been made in our understanding of the intracellular signaling mechanisms in dopamine-related behaviors and pathologies. Through the prism of the regulation of histone H3 and ribosomal protein S6 phosphorylation, we review how dopamine-mediated signaling events regulate gene transcription and mRNA translation...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036296/intracellular-protein-complexes-involved-in-synapse-assembly-in-presynaptic-neurons
#5
Kyung Ah Han, Ji Won Um, Jaewon Ko
The presynaptic active zone, composed of evolutionarily conserved protein complexes, is a specialized area that serves to orchestrate precise and efficient neurotransmitter release by organizing various presynaptic proteins involved in mediating docking and priming of synaptic vesicles, recruiting voltage-gated calcium channels, and modulating presynaptic nerve terminals with aligned postsynaptic structures. Among membrane proteins localized to active zone, presynaptic neurexins and LAR-RPTPs (leukocyte common antigen-related receptor tyrosine phosphatase) have emerged as hubs that orchestrate both shared and distinct extracellular synaptic adhesion pathways...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036295/aquaporin-water-channels-new-perspectives-on-the-potential-role-in-inflammation
#6
Margherita Sisto, Domenico Ribatti, Sabrina Lisi
Aquaporins (AQPs) are a family of membrane water channel proteins that osmotically modulate water fluid homeostasis in several tissues; some of them also transport small solutes such as glycerol. At the cellular level, the AQPs regulate not only cell migration and transepithelial fluid transport across membranes, but also common events that are crucial for the inflammatory response. Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of inflammatory diseases including edematous states, cancer, obesity, wound healing and several autoimmune diseases...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036294/activating-mutations-of-the-gp130-jak-stat-pathway-in-human-diseases
#7
Juliane Lokau, Christoph Garbers
Cytokines of the interleukin-6 (IL-6) family are involved in numerous physiological and pathophysiological processes. Dysregulated and increased activities of its members can be found in practically all human inflammatory diseases including cancer. All cytokines activate several intracellular signaling cascades, including the Jak/STAT, MAPK, PI3K, and Src/YAP signaling pathways. Additionally, several mutations in proteins involved in these signaling cascades have been identified in human patients, which render these proteins constitutively active and result in a hyperactivation of the signaling pathway...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036293/molecular-signaling-in-bone-cells-regulation-of-cell-differentiation-and-survival
#8
Lilian I Plotkin, Angela Bruzzaniti
The achievement of proper bone mass and architecture, and their maintenance throughout life requires the concerted actions of osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells. The differentiation and activity of osteoblasts and osteoclasts are regulated by molecules produced by matrix-embedded osteocytes, as well as by cross talk between osteoblasts and osteoclasts through secreted factors. In addition, it is likely that direct contact between osteoblast and osteoclast precursors, and the contact of these cells with osteocytes and cells in the bone marrow, also modulates bone cell differentiation and function...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036292/relationship-between-mitofusin-2-and-cancer
#9
Alessandro Allegra, Vanessa Innao, Andrea Gaetano Allegra, Caterina Musolino
Mitochondria are dynamic organelles whose actions are fundamental for cell viability. Within the cell, the mitochondrial system is incessantly modified via the balance between fusion and fission processes. Among other proteins, mitofusin 2 is a central protagonist in all these mitochondrial events (fusion, trafficking, contacts with other organelles), the balance of which causes the correct mitochondrial action, shape, and distribution within the cell. Here we examine the structural and functional characteristics of mitofusin 2, underlining its essential role in numerous intracellular pathways, as well as in the pathogenesis of cancer...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036291/intracellular-signaling-of-the-amp-activated-protein-kinase
#10
Miribane Dërmaku-Sopjani, Mentor Sopjani
AMP-activated protein kinase (AMPK) is an essential cellular energy sensor that senses the cellular energy status and maintains cellular energy balance. The AMPK coordinates cellular and whole-body energy homeostasis through stimulating catabolic ATP-producing and suppressing anabolic ATP-consuming intracellular signaling pathways. AMPK induces autophagy and inhibits cell growth in response to starvation, a process that involves regulating certain intracellular signaling molecules. Recent advances demonstrated the AMPK to exert tumor suppressor activity realized through various signaling molecules by stimulating different cellular processes such as apoptosis, autophagy and cell growth and proliferation...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036290/estrogen-receptor-signaling-mechanisms
#11
Nathalie Fuentes, Patricia Silveyra
The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects)...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/31036289/voices-from-the-dead-the-complex-vocabulary-and-intricate-grammar-of-dead-cells
#12
Jerrold S Levine, David S Ucker
Of the roughly one million cells per second dying throughout the body, the vast majority dies by apoptosis, the predominant form of regulated cell death in higher organisms. Long regarded as mere waste, apoptotic cells are now recognized as playing a prominent and active role in homeostatic maintenance, especially resolution of inflammation, and in the sculpting of tissues during development. The activities associated with apoptotic cells are continually expanding, with more recent studies demonstrating their ability to modulate such vital functions as proliferation, survival, differentiation, metabolism, migration, and angiogenesis...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798940/preface
#13
EDITORIAL
Rossen Donev
No abstract text is available yet for this article.
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798939/controlling-the-balance-between-chromosome-break-repair-pathways
#14
Sonia Jimeno, Fernando Mejías-Navarro, Rosario Prados-Carvajal, Pablo Huertas
Broken chromosomes are among the most complex and more difficult to repair DNA lesions. The loss of the continuity of the DNA molecule presents a challenge to the cells, thus the repair of DNA double strand breaks might lead to genomic alterations. Indeed, to minimize this threat to genomic integrity, different DNA repair pathways can act on a broken chromosome. The balance between them is tightly controlled, and it heavily depends on global and local cellular cues. In this chapter, we review our current understanding on the repair of DNA double strand breaks and focus in the regulation of the balance between alternative pathways...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798938/chromatin-control-in-double-strand-break-repair
#15
Anastas Gospodinov, Iva Ugrinova
DNA double strand breaks (DSB) are the most deleterious type of damage inflicted on DNA by various environmental factors and as consequences of normal cellular metabolism. The multistep nature of DSB repair and the need to assemble large protein complexes at repair sites necessitate multiple chromatin changes there. This review focuses on the key findings of how chromatin regulators exert temporal and spatial control on DSB repair. These mechanisms coordinate repair with cell cycle progression, lead to DSB repair pathway choice, provide accessibility of repair machinery to damaged sites and move the lesions to nuclear environments permissive for repair...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798937/a-computational-model-to-predict-the-structural-and-functional-consequences-of-missense-mutations-in-o-6-methylguanine-dna-methyltransferase
#16
D Thirumal Kumar, Enid Mendonca, J Priyadharshini Christy, C George Priya Doss, Hatem Zayed
DNA repair mechanism is a process through which the cell repairs its damaged DNA. Although there are several mechanisms involved in the DNA repair mechanisms, the direct reversal method is the simplest and does not require a reference template, in which the guanine bases are often methylated, and the methyl guanine methyl transferase protein (MGMT) reverses them. The mutations occurring in the MGMT protein might result in dysfunction of such DNA repair mechanism. In this study, we attempted to evaluate the impact of six missense mutations (Y114E, Y114A, R128G, R128A, R128K, and C145A) at three active-site positions (Y114, C145, and R128) as this might hinder the DNA binding to the protein...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798936/elucidating-the-role-of-interacting-residues-of-the-msh2-msh6-complex-in-dna-repair-mechanism-a-computational-approach
#17
D Thirumal Kumar, B Susmita, E Judith, J Priyadharshini Christy, C George Priya Doss, Hatem Zayed
The DNA repair system is crucial to repair the error resulting in DNA replication. MSH2-MSH6 protein complex plays a significant role in maintaining the mismatch repair mechanism. Mutations in the interface between the two proteins compromise their function in the repair process. The present study aims to understand the impact of missense mutations in the interacting sites of the MSH2-MSH6 protein complex. MSH6 is unstable due to the disordered N-terminal domain. This is stabilized by the MSH2 hetero-dimerization...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798935/mechanistic-link-between-dna-damage-sensing-repairing-and-signaling-factors-and-immune-signaling
#18
Shibani Mukherjee, Salim Abdisalaam, Souparno Bhattacharya, Kalayarasan Srinivasan, Debapriya Sinha, Aroumougame Asaithamby
Previously, DNA damage sensing, repairing and signaling machineries were thought to mainly suppress genomic instability in response to genotoxic stress. Emerging evidence indicates a crosstalk between DNA repair machinery and the immune system. In this chapter, we attempt to decipher the molecular choreography of how factors, including ATM, BRCA1, DNA-PK, FANCA/D2, MRE11, MUS81, NBS1, RAD51 and TREX1, of multiple DNA metabolic processes are directly or indirectly involved in suppressing cytosolic DNA sensing pathway-mediated immune signaling...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798934/camp-mediated-regulation-of-melanocyte-genomic-instability-a-melanoma-preventive-strategy
#19
Nathaniel C Holcomb, Robert-Marlo Bautista, Stuart G Jarrett, Katharine M Carter, Madeline Krentz Gober, John A D'Orazio
Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage...
2019: Advances in Protein Chemistry and Structural Biology
https://read.qxmd.com/read/30798933/tfiih-a-multi-subunit-complex-at-the-cross-roads-of-transcription-and-dna-repair
#20
Olga Kolesnikova, Laura Radu, Arnaud Poterszman
Transcription factor IIH (TFIIH) is a multiprotein complex involved in both eukaryotic transcription and DNA repair, revealing a tight connection between these two processes. Composed of 10 subunits, it can be resolved into a 7-subunits core complex with the XPB translocase and the XPD helicase, and the 3-subunits kinase complex CAK, which also exists as a free complex with a distinct function. Initially identified as basal transcription factor, TFIIH also participates in transcription regulation and plays a key role in nucleotide excision repair (NER) for opening DNA at damaged sites, lesion verification and recruitment of additional repair factors...
2019: Advances in Protein Chemistry and Structural Biology
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