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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11232

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Special Issue Editors

Prof. Dr. Shengce Tao

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Guest Editor

Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
Interests: microarrays; antibodies; protein-protein interactions; virus

Prof. Dr. Chunfu Zhang

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Guest Editor

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Interests: nano materials

Prof. Dr. Haijie Han

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Guest Editor

School of Medicine, Zhejiang University, Hangzhou 310009, China
Interests: ocular drug delivery; dry eye

Dr. Yin Wang

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Guest Editor

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Interests: peptide and peptide-drug conjugates; gasotransmitters delivery and therapy; supramolecular self-assembly; biomaterials; reactive oxygen species
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Prof. Dr. Daniel M. Czajkowsky

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Guest Editor

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Interests: 3D chromatin structure; Hi-C; nucleosome positioning; super-resolution optical microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Macromolecules perform many of the most fundamentally important functions in biology. They are the antibodies that are produced to quell foreign pathogens, the mRNA that is first transcribed and then translated to generate the proteomic repertoire of each cell, and the chromatin that ultimately determines the cell’s phenotype. As such, the study of their identity, composition, structure, interacting partners, and functioning mechanisms is one of the most active fields of scientific study both in China and around the world. However, as we learn of these basic properties, we also discover that they can be re-imagined to function in novel biotechnological or biomedical applications. Moreover, with this understanding, we find that they can serve as the inspiration for the rational design of synthetic macromolecules to mimic their behaviors for biotechnological applications or to interface with possible therapies in clinical settings. Thus, whether to further our understanding of basic biological processes or for biotechnological/biomedical applications, macromolecules are at the nexus of much of the most important present-day research in biology.

With this Special Issue of IJMS, we hope to highlight and exemplify the present state-of-the-art in the research of biological and synthetic macromolecules in both basic biological studies as well as biotechnological and biomedical applications in China. We, the Guest Editors, welcome and encourage all submissions from researchers in China who are contributing to this incredibly vigorous area of research.

Prof. Dr. Shengce Tao
Prof. Dr. Chunfu Zhang
Prof. Dr. Haijie Han
Dr. Yin Wang
Prof. Dr. Daniel M. Czajkowsky
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

proteins (especially, antibodies, condensates, and protein engineering)
peptides
RNA
chromatin
DNA biotechnology
synthetic bio-mimics or therapeutics
drug carriers or nanomedicine

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Research

14 pages, 1994 KiB

Open AccessCommunication

Quantitative Super-Resolution Microscopy Reveals the Relationship between CENP-A Stoichiometry and Centromere Physical Size

by Yaqian Li, Jiabin Wang, Xuecheng Chen, Daniel M. Czajkowsky and Zhifeng Shao

Int. J. Mol. Sci. 2023, 24(21), 15871; https://doi.org/10.3390/ijms242115871 - 1 Nov 2023

Cited by 1 | Viewed by 1632

Abstract

Centromeric chromatin is thought to play a critical role in ensuring the faithful segregation of chromosomes during mitosis. However, our understanding of this role is presently limited by our poor understanding of the structure and composition of this unique chromatin. The nucleosomal variant, CENP-A, localizes to narrow regions within the centromere, where it plays a major role in centromeric function, effectively serving as a platform on which the kinetochore is assembled. Previous work found that, within a given cell, the number of microtubules within kinetochores is essentially unchanged between CENP-A-localized regions of different physical sizes. However, it is unknown if the amount of CENP-A is also unchanged between these regions of different sizes, which would reflect a strict structural correspondence between these two key characteristics of the centromere/kinetochore assembly. Here, we used super-resolution optical microscopy to image and quantify the amount of CENP-A and DNA within human centromere chromatin. We found that the amount of CENP-A within CENP-A domains of different physical sizes is indeed the same. Further, our measurements suggest that the ratio of CENP-A- to H3-containing nucleosomes within these domains is between 8:1 and 11:1. Thus, our results not only identify an unexpectedly strict relationship between CENP-A and microtubules stoichiometries but also that the CENP-A centromeric domain is almost exclusively composed of CENP-A nucleosomes. Full article

(This article belongs to the Special Issue State-of-the-Art Macromolecules in China)

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20 pages, 4940 KiB

Open AccessArticle

ARHGAP11A Is a Novel Prognostic and Predictive Biomarker Correlated with Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma

by Huihui Yang, Hongning Zhang, Liuxu Zhang, Paizigul Tusuphan and Junfang Zheng

Int. J. Mol. Sci. 2023, 24(9), 7755; https://doi.org/10.3390/ijms24097755 - 24 Apr 2023

Cited by 6 | Viewed by 2168

Abstract

Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor and immune dysfunction is associated with ccRCC poor prognosis. The RhoGTPase-activating proteins (RhoGAPs) family was reported to affect ccRCC development, but its role in immunity and prognosis prediction for ccRCC remain unknown. In the current study, we found ARHGAP11A was the only independent risk factor among 33 RhoGAPs (hazard ratio [HR] 1.949, 95% confidence interval [CI] 1.364–2.785). High ARHGAP11A level was associated with shorter overall survival (OS, HR 2.040, 95% CI 1.646–3.417) and ARHGAP11A is a prognostic biomarker for ccRCC. ARHGAP11A knockdown suppressed renal cell carcinoma (RCC) cell proliferation, colony formation, and migration, suggesting the promoting role of ARHGAP11A on RCC development. Mechanistically, ARHGAP11A might contribute to the suppressive tumor immune microenvironment (TIME). High ARHGAP11A level was correlated with infiltration of immunosuppressive cells (including T helper 2 (Th2) cells, regulatory T (Treg) cells, myeloid derived suppressor cells (MDSC), and M2 macrophage cells), activation of immunosuppressive pathways (IL6-JAK-STAT3 signaling and IFNγ response), and expression of inhibitory immune checkpoints (ICs). ARHGAP11A could promote T cell exhaustion and induce immune escape. ccRCC patients with low ARHGAP11A level were more suitable for immune checkpoint inhibitors (ICIs) therapy, while those with high ARHGAP11A level might benefit from a combination of ARHGAP11A blockade and ICIs. In all, ARHGAP11A might serve as a novel prognostic marker, therapeutic target, and predictor in the clinical response to ICIs therapy for ccRCC. Full article

(This article belongs to the Special Issue State-of-the-Art Macromolecules in China)

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14 pages, 1314 KiB

Open AccessArticle

Temporal Analysis Reveals the Transient Differential Expression of Transcription Factors That Underlie the Trans-Differentiation of Human Monocytes to Macrophages

by Weihang Deng, Min Chen, Ying Tang, Le Zhang, Zeqian Xu, Xinhui Li, Daniel M. Czajkowsky and Zhifeng Shao

Int. J. Mol. Sci. 2022, 23(24), 15830; https://doi.org/10.3390/ijms232415830 - 13 Dec 2022

Cited by 1 | Viewed by 1790

Abstract

The activation of monocytes and their trans-differentiation into macrophages are critical processes of the immune response. Prior work has characterized the differences in the expression between monocytes and macrophages, but the transitional process between these cells is poorly detailed. Here, we analyzed the temporal changes of the transcriptome during trans-differentiation of primary human monocytes into M0 macrophages. We find changes with many transcription factors throughout the process, the vast majority of which exhibit a maximally different expression at the intermediate stages. A few factors, including AP-1, were previously known to play a role in immunological transitions, but most were not. Thus, these findings indicate that this trans-differentiation requires the dynamic expression of many transcription factors not previously discussed in immunology, and provide a foundation for the delineation of the molecular mechanisms associated with healthy or pathological responses that involve this transition. Full article

(This article belongs to the Special Issue State-of-the-Art Macromolecules in China)

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18 pages, 6121 KiB

Open AccessArticle

Activation Mechanism of RhoA Caused by Constitutively Activating Mutations G14V and Q63L

by Shiyao Chen, Zirui Zhang, Yijing Zhang, Taeyoung Choi and Yaxue Zhao

Int. J. Mol. Sci. 2022, 23(24), 15458; https://doi.org/10.3390/ijms232415458 - 7 Dec 2022

Cited by 2 | Viewed by 2088

Abstract

RhoA, a member of Rho GTPases, regulates myriad cellular processes. Abnormal expression of RhoA has been implicated in various diseases, including cancers, developmental disorders and bacterial infections. RhoA mutations G14V and Q63L have been reported to constitutively activate RhoA. To figure out the mechanisms, in total, 1.8 μs molecular dynamics (MD) simulations were performed here on RhoA^WT and mutants G14V and Q63L in GTP-bound forms, followed by dynamic analysis. Both mutations were found to affect the conformational dynamics of RhoA switch regions, especially switch I, shifting the whole ensemble from the wild type’s open inactive state to different active-like states, where T37 and Mg²⁺ played important roles. In RhoA^G14V, both switches underwent thorough state transition, whereas in RhoA^Q63L, only switch I was sustained in a much more closed conformation with additional hydrophobic interactions introduced by L63. Moreover, significantly decreased solvent exposure of the GTP-binding site was observed in both mutants with the surrounding hydrophobic regions expanded, which furnished access to water molecules required for hydrolysis more difficult and thereby impaired GTP hydrolysis. These structural and dynamic differences first suggested the potential activation mechanism of RhoA^G14V and RhoA^Q63L. Together, our findings complemented the understanding of RhoA activation at the atomic level and can be utilized in the development of novel therapies for RhoA-related diseases. Full article

(This article belongs to the Special Issue State-of-the-Art Macromolecules in China)

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23 pages, 10623 KiB

Open AccessArticle

Comprehensive Analysis of Arabinogalactan Protein-Encoding Genes Reveals the Involvement of Three BrFLA Genes in Pollen Germination in Brassica rapa

by Huiting Huang, Yingjing Miao, Yuting Zhang, Li Huang, Jiashu Cao and Sue Lin

Int. J. Mol. Sci. 2021, 22(23), 13142; https://doi.org/10.3390/ijms222313142 - 5 Dec 2021

Cited by 4 | Viewed by 2423

Abstract

Arabinogalactan proteins (AGPs) are a superfamily of hydroxyproline-rich glycoproteins that are massively glycosylated, widely implicated in plant growth and development. No comprehensive analysis of the AGP gene family has been performed in Chinese cabbage (Brassica rapa ssp. chinensis). Here, we identified a total of 293 putative AGP-encoding genes in B. rapa, including 25 classical AGPs, three lysine-rich AGPs, 30 AG-peptides, 36 fasciclin-like AGPs (FLAs), 59 phytocyanin-like AGPs, 33 xylogen-like AGPs, 102 other chimeric AGPs, two non-classical AGPs and three AGP/extensin hybrids. Their protein structures, phylogenetic relationships, chromosomal location and gene duplication status were comprehensively analyzed. Based on RNA sequencing data, we found that 73 AGP genes were differentially expressed in the floral buds of the sterile and fertile plants at least at one developmental stage in B. rapa, suggesting a potential role of AGPs in male reproductive development. We further characterized BrFLA2, BrFLA28 and BrFLA32, three FLA members especially expressed in anthers, pollen grains and pollen tubes. BrFLA2, BrFLA28 and BrFLA32 are indispensable for the proper timing of pollen germination under high relative humidity. Our study greatly extends the repertoire of AGPs in B. rapa and reveals a role for three members of the FLA subfamily in pollen germination. Full article

(This article belongs to the Special Issue State-of-the-Art Macromolecules in China)

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