AIMS BiophysicsPub Date : 2016-01-01Epub Date: 2016-02-28DOI: 10.3934/biophy.2016.1.99
Marek K Korzeniowski, Barbara Baird, David Holowka
{"title":"STIM1 activation is regulated by a 14 amino acid sequence adjacent to the CRAC activation domain.","authors":"Marek K Korzeniowski, Barbara Baird, David Holowka","doi":"10.3934/biophy.2016.1.99","DOIUrl":"https://doi.org/10.3934/biophy.2016.1.99","url":null,"abstract":"<p><p>Oligomerization of the Ca<sup>2+</sup> sensor, STIM1, in the endoplasmic reticulum (ER) membrane, caused by depletion of ER Ca<sup>2+</sup> stores, results in STIM1 coupling to the plasma membrane Ca<sup>2+</sup> channel protein, Orai1, to activate Ca<sup>2+</sup> influx in a process known as store-operated Ca<sup>2+</sup> entry. We use fluorimetry-based fluorescence resonance energy transfer (FRET) to monitor changes in STIM1 oligomerization in COS7 cells transfected with STIM1 constructs containing selected truncations, deletions, and point mutations, and labeled with donor and acceptor fluorescent proteins at either the luminal (N-terminal) or the cytoplasmic (C-terminal) ends. Our results with sequential truncations of STIM1 from the C-terminus support previous evidence that the CRAC activation domain (CAD/SOAR, human sequence 342-448) is an oligomer-promoting segment of STIM1, and they show that truncation just after CAD/SOAR (1-448) causes significantly elevated basal cytoplasmic Ca<sup>2+</sup> and spontaneous STIM1 clustering. We find that a 14 amino acid sequence just C-terminal of CAD/SOAR (449-462) prevents spontaneous clustering and activation of STIM1 in COS7 cells. In response to store depletion, C-terminally labeled STIM1 without CAD/SOAR clusters together with CAD/SOAR-containing STIM1 constructs. However, these donor-acceptor pairs do not undergo a stimulated increase in FRET, exhibiting instead a decrease in FRET consistent with a stimulated conformational extension in full length STIM1. We find that the 14 amino acid sequence plays a regulatory role in this process. Overall, our FRET results provide evidence in live cells that Ca<sup>2+</sup> store depletion stimulates a conformational extension in the cytoplasmic segment of STIM1 that accompanies its oligomerization.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"3 1","pages":"99-118"},"PeriodicalIF":1.5,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34529987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2016-01-01Epub Date: 2016-03-09DOI: 10.3934/biophy.2016.1.195
Riyaz A Mir, Jeff Lovelace, Nicholas P Schafer, Peter D Simone, Admir Kellezi, Carol Kolar, Gaelle Spagnol, Paul L Sorgen, Hamid Band, Vimla Band, Gloria E O Borgstahl
{"title":"Biophysical characterization and modeling of human Ecdysoneless (ECD) protein supports a scaffolding function.","authors":"Riyaz A Mir, Jeff Lovelace, Nicholas P Schafer, Peter D Simone, Admir Kellezi, Carol Kolar, Gaelle Spagnol, Paul L Sorgen, Hamid Band, Vimla Band, Gloria E O Borgstahl","doi":"10.3934/biophy.2016.1.195","DOIUrl":"https://doi.org/10.3934/biophy.2016.1.195","url":null,"abstract":"<p><p>The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse <i>Ecd</i> is early embryonic lethal and <i>Ecd</i> deletion delays G<sub>1</sub>-S cell cycle progression. Importantly, ECD directly interacts with the Rb tumor suppressor and competes with the E2F transcription factor for binding to Rb. Further studies demonstrated ECD is overexpressed in breast and pancreatic cancers and its overexpression correlates with poor patient survival. ECD overexpression together with Ras induces cellular transformation through upregulation of autophagy. Recently we demonstrated that CK2 mediated phosphorylation of ECD and interaction with R2TP complex are important for its cell cycle regulatory function. Considering that ECD is a component of multiprotein complexes and its crystal structure is unknown, we characterized ECD structure by circular dichroism measurements and sequence analysis software. These analyses suggest that the majority of ECD is composed of α-helices. Furthermore, small angle X-ray scattering (SAXS) analysis showed that deletion fragments, ECD(1-432) and ECD(1-534), are both well-folded and reveals that the first 400 residues are globular and the next 100 residues are in an extended cylindrical structure. Taking all these results together, we speculate that ECD acts like a structural hub or scaffolding protein in its association with its protein partners. In the future, the hypothetical model presented here for ECD will need to be tested experimentally.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"3 1","pages":"195-208"},"PeriodicalIF":1.5,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34984826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01Epub Date: 2015-12-01DOI: 10.3934/biophy.2015.4.794
Michael J Hamilton, Matthew D Young, Silvia Sauer, Ernest Martinez
{"title":"The interplay of long non-coding RNAs and MYC in cancer.","authors":"Michael J Hamilton, Matthew D Young, Silvia Sauer, Ernest Martinez","doi":"10.3934/biophy.2015.4.794","DOIUrl":"10.3934/biophy.2015.4.794","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 4","pages":"794-809"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34314337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01DOI: 10.3934/biophy.2015.1.21
J Bernard Heymann
{"title":"Validation of 3D EM Reconstructions: The Phantom in the Noise.","authors":"J Bernard Heymann","doi":"10.3934/biophy.2015.1.21","DOIUrl":"https://doi.org/10.3934/biophy.2015.1.21","url":null,"abstract":"<p><p>Validation is a necessity to trust the structures solved by electron microscopy by single particle techniques. The impressive achievements in single particle reconstruction fuel its expansion beyond a small community of image processing experts. This poses the risk of inappropriate data processing with dubious results. Nowhere is it more clearly illustrated than in the recovery of a reference density map from pure noise aligned to that map-a phantom in the noise. Appropriate use of existing validating methods such as resolution-limited alignment and the processing of independent data sets (\"gold standard\") avoid this pitfall. However, these methods can be undermined by biases introduced in various subtle ways. How can we test that a map is a coherent structure present in the images selected from the micrographs? In stead of viewing the phantom emerging from noise as a cautionary tale, it should be used as a defining baseline. Any map is always recoverable from noise images, provided a sufficient number of images are aligned and used in reconstruction. However, with smaller numbers of images, the expected coherence in the real particle images should yield better reconstructions than equivalent numbers of noise or background images, even without masking or imposing resolution limits as potential biases. The validation test proposed is therefore a simple alignment of a limited number of micrograph and noise images against the final reconstruction as reference, demonstrating that the micrograph images yield a better reconstruction. I examine synthetic cases to relate the resolution of a reconstruction to the alignment error as a function of the signal-to-noise ratio. I also administered the test to real cases of publicly available data. Adopting such a test can aid the microscopist in assessing the usefulness of the micrographs taken before committing to lengthy processing with questionable outcomes.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 1","pages":"21-35"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33332473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01Epub Date: 2015-10-19DOI: 10.3934/biophy.2015.4.555
Qiao Yi Chen, Max Costa, Hong Sun
{"title":"Structure and function of histone acetyltransferase MOF.","authors":"Qiao Yi Chen, Max Costa, Hong Sun","doi":"10.3934/biophy.2015.4.555","DOIUrl":"10.3934/biophy.2015.4.555","url":null,"abstract":"<p><p>MOF was first identified in <i>Drosophila melanogaster</i> as an important component of the dosage compensation complex. As a member of MYST family of histone acetyltransferase, MOF specifically deposits the acetyl groups to histone H4 lysine 16. Throughout evolution, MOF and its mammalian ortholog have retained highly conserved substrate specificity and similar enzymatic activities. MOF plays important roles in dosage compensation, ESC self-renewal, DNA damage and repair, cell survival, and gene expression regulation. Dysregulation of MOF has been implicated in tumor formation and progression of many types of human cancers. This review will discuss the structure and activity of mammalian hMOF as well as its function in H4K16 acetylation, DNA damage response, stem cell pluripotency, and carcinogenesis.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 4","pages":"555-569"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425159/pdf/nihms825743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34995608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01Epub Date: 2015-11-16DOI: 10.3934/biophy.2015.4.724
Missag Hagop Parseghian
{"title":"What is the role of histone H1 heterogeneity? A functional model emerges from a 50 year mystery.","authors":"Missag Hagop Parseghian","doi":"10.3934/biophy.2015.4.724","DOIUrl":"10.3934/biophy.2015.4.724","url":null,"abstract":"<p><p>For the past 50 years, understanding the function of histone H1 heterogeneity has been mired in confusion and contradiction. Part of the reason for this is the lack of a working model that tries to explain the large body of data that has been collected about the H1 subtypes so far. In this review, a global model is described largely based on published data from the author and other researchers over the past 20 years. The intrinsic disorder built into H1 protein structure is discussed to help the reader understand that these histones are multi-conformational and adaptable to interactions with different targets. We discuss the role of each structural section of H1 (as we currently understand it), but we focus on the H1's C-terminal domain and its effect on each subtype's affinity, mobility and compaction of chromatin. We review the multiple ways these characteristics have been measured from circular dichroism to FRAP analysis, which has added to the sometimes contradictory assumptions made about each subtype. Based on a tabulation of these measurements, we then organize the H1 variants according to their ability to condense chromatin and produce nucleosome repeat lengths amenable to that compaction. This subtype variation generates a continuum of different chromatin states allowing for fine regulatory control and some overlap in the event one or two subtypes are lost to mutation. We also review the myriad of disparate observations made about each subtype, both somatic and germline specific ones, that lend support to the proposed model. Finally, to demonstrate its adaptability as new data further refines our understanding of H1 subtypes, we show how the model can be applied to experimental observations of telomeric heterochromatin in aging cells.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 4","pages":"724-772"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37404891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01Epub Date: 2015-06-17DOI: 10.3934/biophy.2015.2.200
Z Hong Zhou, Joshua Chiou
{"title":"Protein chainmail variants in dsDNA viruses.","authors":"Z Hong Zhou, Joshua Chiou","doi":"10.3934/biophy.2015.2.200","DOIUrl":"https://doi.org/10.3934/biophy.2015.2.200","url":null,"abstract":"First discovered in bacteriophage HK97, biological chainmail is a highly stable system formed by concatenated protein rings. Each subunit of the ring contains the HK97-like fold, which is characterized by its submarine-like shape with a 5-stranded β sheet in the axial (A) domain, spine helix in the peripheral (P) domain, and an extended (E) loop. HK97 capsid consists of covalently-linked copies of just one HK97-like fold protein and represents the most effective strategy to form highly stable chainmail needed for dsDNA genome encapsidation. Recently, near-atomic resolution structures enabled by cryo electron microscopy (cryoEM) have revealed a range of other, more complex variants of this strategy for constructing dsDNA viruses. The first strategy, exemplified by P22-like phages, is the attachment of an insertional (I) domain to the core 5-stranded β sheet of the HK97-like fold. The atomic models of the Bordetella phage BPP-1 showcases an alternative topology of the classic HK97 topology of the HK97-like fold, as well as the second strategy for constructing stable capsids, where an auxiliary jellyroll protein dimer serves to cement the non-covalent chainmail formed by capsid protein subunits. The third strategy, found in lambda-like phages, uses auxiliary protein trimers to stabilize the underlying non-covalent chainmail near the 3-fold axis. Herpesviruses represent highly complex viruses that use a combination of these strategies, resulting in four-level hierarchical organization including a non-covalent chainmail formed by the HK97-like fold domain found in the floor region. A thorough understanding of these structures should help unlock the enigma of the emergence and evolution of dsDNA viruses and inform bioengineering efforts based on these viruses.","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 2","pages":"200-218"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35586725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 2015-01-01Epub Date: 2015-08-18DOI: 10.3934/biophy.2015.3.343
Wei Zhang, Sheng Cao, Jessica L Martin, Joachim D Mueller, Louis M Mansky
{"title":"Morphology and ultrastructure of retrovirus particles.","authors":"Wei Zhang, Sheng Cao, Jessica L Martin, Joachim D Mueller, Louis M Mansky","doi":"10.3934/biophy.2015.3.343","DOIUrl":"https://doi.org/10.3934/biophy.2015.3.343","url":null,"abstract":"<p><p>Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell.</p>","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"2 3","pages":"343-369"},"PeriodicalIF":1.5,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3934/biophy.2015.3.343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34139225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 1900-01-01DOI: 10.3934/biophy.2022020
Yong Zhou, Yiming Ding
{"title":"Finding travel proportion under COVID-19","authors":"Yong Zhou, Yiming Ding","doi":"10.3934/biophy.2022020","DOIUrl":"https://doi.org/10.3934/biophy.2022020","url":null,"abstract":"\u0000Travel restrictions have become an important epidemic preventive measure, but there are few relevant quantitative studies. In this paper, travel proportion is introduced into a four-compartment model to quantify the spread of COVID-19 in Wuhan. It is found that decreasing the travel proportion can reduce the peak of infections and delay the peak time. When the travel proportion is less than 35%, transmission can be prevented. This method provides reference for other places.\u0000","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"1 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70185492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS BiophysicsPub Date : 1900-01-01DOI: 10.3934/biophy.2022012
L. Krasnobaeva, L. Yakushevich
{"title":"DNA kinks behavior in the potential pit-trap","authors":"L. Krasnobaeva, L. Yakushevich","doi":"10.3934/biophy.2022012","DOIUrl":"https://doi.org/10.3934/biophy.2022012","url":null,"abstract":"\u0000For better understanding the role of dynamic factors in the DNA functioning, it is important to study the internal mobility of DNA and, in particular, the movement of nonlinear conformational distortions -kinks along the DNA chains. In this work, we study the behavior of the kinks in the pPF1 plasmid containing two genes of fluorescent proteins (EGFP and mCherry). To simulate the movement, two coupled nonlinear sine-Gordon equations that describe the angular oscillations of nitrogenous bases in the main and complementary chains and take into account the effects of dissipation and the action of a constant torsion field. To solve the equations, approximate methods such as the quasi-homogeneous approximation, the mean field method, and the block method, were used. The obtained solutions indicate that two types of kinks moving along the double strand can be formed in any part of the plasmid. The profiles of the potential fields in which these kinks are moving are calculated. The results of the calculations show that the lowest energy required for the kink formation, corresponds to the region located between the genes of green and red proteins (EGFP and mCherry). It is shown that it is in this region a pit trap is located for both kinks. Trajectories of the kinks in the pit-trap and nearby are constructed. It is shown that there are threshold values of the torsion field, upon reaching which the kinks behavior changes dramatically: there is a transition from cyclic motion inside the pit-trap to translational motion and exit from the potential pit-trap.\u0000","PeriodicalId":7529,"journal":{"name":"AIMS Biophysics","volume":"1 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70185031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}