Intrinsically Disordered Proteins: An Overview

Trivedi, Rakesh; Nagarajaram, Hampapathalu A.

doi:10.3390/ijms232214050

Cited by 60 publications

(48 citation statements)

References 361 publications

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“…The SCL-S protein is composed of the bHLH domain and the C-terminal domain. The intrinsically disordered regions (IDRs) have been deeply explored in recent years [ 37 , 38 ]. It is common rather than unusual for transcription factors to contain IDRs [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of SCL Isoforms in Embryonic Hematopoiesis

Chuang

Chen

et al. 2023

IJMS

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Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The SCLΔ/Δ homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34+ and CD43+ cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5 SCLΔ/Δ embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.

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Section: Discussionmentioning

confidence: 99%

The Role of SCL Isoforms in Embryonic Hematopoiesis

Chuang

Chen

et al. 2023

IJMS

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“…It is a well-known fact that it is the structure of a molecule, especially if it is a protein, that determines and dictates its function. However, it must be taken into account that some proteins have an intrinsically disordered structure and yet perform their function without hindrance (intrinsically disordered proteins) [ 67 , 68 ]. In the case of blood coagulation, an initial signal, i.e., endothelial damage, is exponentially amplified by the presence of zymogens or precursor proteins that are irreversibly activated by the action of proteases [ 69 , 70 ].…”

Section: Factor V a Procoagulant And Anticoagulant Proteinmentioning

confidence: 99%

The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency

Pablo-Moreno

Miguel-Batuecas

Sancha

et al. 2023

IJMS

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Proteostasis, i.e., the homeostasis of proteins, responsible for ensuring protein turnover, is regulated by proteases, which also participate in the etiopathogenesis of multiple conditions. The magic of proteases is such that, in blood coagulation, one same molecule, such as coagulation factor V, for example, can perform both a procoagulant and an anticoagulant function as a result of the activity of proteases. However, this magic has an insidious side to it, as it may also prevent the completion of the clinical value chain of factor V deficiency. This value chain encompasses the discovery of knowledge, the transfer of this knowledge, and its translation to clinical practice. In the case of rare and ultra-rare diseases like factor V deficiency, this value chain has not been completed as the knowledge acquisition phase has dragged out over time, holding up the transfer of knowledge to clinical practice. The reason for this is related to the small number of patients afflicted with these conditions. As a result, new indications must be found to make the therapies cost-effective. In the case of factor V, significant research efforts have been directed at developing a recombinant factor V capable of resisting the action of the proteases capable of inactivating this factor. This is where bioethics and health equity considerations come into the equation.

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“…How could a chimeric peptide-antigen be generated? I propose as a source a complex of two assembling IDPs or IDPRs 57,58,59 . Such complexes are formed upon treatment of E. coli with antimicrobial peptide fragments of the IDP hornerin (HRNR).…”

Section: Psoriasis Serum Contains Bispecific Antibodies Towards C Sim...mentioning

confidence: 99%

Discovery of Natural Bispecific Antibodies: Is Psoriasis Induced by a ToxigenicCorynebacterium simulansand Maintained by CIDAMPs as Autoantigens?

Schröder

2023

Preprint

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The high abundance of Corynebacterium simulans in psoriasis skin suggests a contribution to the psoriasis etiology via cell envelope components, which may cause skin inflammation and immune responses. This hypothesis was tested in an exploratory study, where Western Blot (WB) analyses with extracts of heat-treated C. simulans and psoriasis serum-derived IgG exhibited a single 16 kDa-WB-band. Proteomic analyses revealed, among others, ribosomal proteins as candidate C. s.-antigens. A peptidomic analysis unexpectedly showed that psoriasis-serum-derived IgG already contained 31 immunopeptides originating from Corynebacteria ssp., suggesting the presence of natural bispecific antibodies (BsAbs). Moreover, peptidomic analyses revealed 372 DECOY-peptides with similarity to virus- and phage proteins, including Corynebacterium diphtheriae phage, and similarity to diphtheria toxin. Strikingly, upon a peptidomic analysis for peptides of human origin, 64 epitopes of major psoriasis autoantigens were identified, which originated from the spacer region of filaggrin, from hornerin repeats, SPINK9, keratin 9, caspase 14, desmoplakin, suprabasin, keratin 2, keratin1, keratin 6C, apolipoprotein A1, a Selene-binding protein, H1.8 linker histone, and the transcription factor BCLAF3. Most identified antigens represent potential Cationic Intrinsically Disordered Antimicrobial Peptides (CIDAMPs), which are generated within the fully differentiated epidermis. These may form complexes with bacterial disordered protein regions, representing chimeric antigens containing discontinuous epitopes. In addition, among 128 low-abundance immunopeptides, 48 are putatively psoriasis-relevant such as epitopes of IL-12, and the receptors of PGE2, vitamin D3, and IL-10. Further, 47 immunopeptides originated from tumor antigens such as CT47A, SDCCAG3, BRCA2, MAGEA6, RNASE4, and the endogenous retrovirus HERV-K. I propose that persistent infection with a toxigenic C. simulans initiates psoriasis, which is exacerbated as an autoimmune disease by CIDAMPs as autoantigens. The discovery of natural BsAbs allows the identification of antigen epitopes from microbes, viruses, autoantigens, and tumor-antigens, and may help to develop epitope-specific peptide-vaccines and therapeutic approaches with antigen-specific regulatory T cells to improve immune tolerance in an autoimmune disease-specific-manner.

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Intrinsically Disordered Proteins: An Overview

Cited by 60 publications

References 361 publications

The Role of SCL Isoforms in Embryonic Hematopoiesis

The Role of SCL Isoforms in Embryonic Hematopoiesis

The Magic of Proteases: From a Procoagulant and Anticoagulant Factor V to an Equitable Treatment of Its Inherited Deficiency

Discovery of Natural Bispecific Antibodies: Is Psoriasis Induced by a ToxigenicCorynebacterium simulansand Maintained by CIDAMPs as Autoantigens?

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