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Beta Cells and Diabetes
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nutraceuticals and Dietary Supplements, 2020
Shivani Srivastava, Durgavati Yadav, Kumar Sandeep, Harsh Pandey, Surya Kumar Singh, Yamini Bhusan Tripathi
Many human disorders like Alzheimer’s, Parkinson’s, and T2D have a relation with amyloid deposition. It is the partially ordered fibrillar protein aggregated rich in beta sheets structure. In T2D, islets amyloid is usually formed by a neuropancreatic hormone islet amyloid polypeptide (IAPP), also known as amylin. This formation leads to β cells dysfunction and death. Interestingly, amyloid formation does not occur in all species. Cats, humans, and nonhuman primates develop islet amyloid formation but mice and rats do not. IAPP is secreted with insulin secretion, which means it is absent in TIDM. Reduced expression and reduction of IAPP in TIDM and later stage of T2DM usually leads to deleterious effect. But the case of T2DM is different, here the toxicity induced by amyloidosis is one of the major concerns. Heparansulfate proteoglycan perlecan, apolipoprotein E, and serum amyloid P component are the constituents of islet amyloid (Abedini et al., 2015).
Disease Prediction and Drug Development
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
There are two types of secondary structures: α-helix and β-sheet. Alpha-helix is a right-handed helical structure that is maintained using a hydrogen-bond between N–H group and C=O group of four amino-acid residue occurring earlier. Beta-sheet is pleated and consists of three to ten polypeptides-strands. A strand in a β-sheet is connected to the adjacent strand in a lateral direction using hydrogen-bonds.
The Single-Stranded DNA Binding Protein of Bacteriophage T4
Published in James F. Kane, Multifunctional Proteins: Catalytic/Structural and Regulatory, 2019
Daniel H. Doherty, Peter Gauss, Larry Gold
On the basis of secondary structure predictions, Williams et al.37 suggested that gp32 could be divided into 3 domains. The aminoterminal region (residues 1 to 35) and the carboxyterminal region (residues 187 to 301) are each primarily alpha-helical. The central region of the protein (residues 36 to 186) contains most of the beta sheet structures and beta turns. These investigators pointed out some interesting features of the region around residues 72 through 116. This region contains 6 of the 8 tyrosine residues found in the protein and 5 of these are nearly equally spaced in the primary structure. This region is predicted to be composed of three- short beta sheets separated by beta turns. This predicted secondary structure is similar to the actual structure of the DNA binding site of the ssDNA binding protein of bacteriophage fd. As determined by X-ray crystallography at 2.3 A resolution, the bulk of the amino acid residues that interact with ssDNA reside in a three-stranded beta structure comprised of about 40 residues.43 This beta structure contains several aromatic residues which could interact with bound DNA by intercalation. Indeed, in the case of the fd ssDNA binding protein, tyrosine intercalation is known to be involved in DNA binding.44 In the case of gp32, there is also some indication that tyrosine intercalation may be involved in DNA binding.46
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
The higher-order structure of antibodies also plays a crucial role in the risk for Asp isomerization. Dihedral angles can influence the reactivity of Asp residues and affect the risk of isomerization.26 Diepold and colleagues observed isomerization for liable motifs within the solvent-exposed and flexible CDR loops. However, isomerization did not occur at the DG motif in the conserved region of the antibody.45 Asp isomerization is the least favorable within beta-sheets due to structural rigidity. Sreedhara and colleagues observed succinimide formation for Asp74, which was solvent-exposed and part of a loop, whereas the Asp73 within beta-helix was less prone to isomerization.40 In addition, hydrogen bonding for peptide backbone and side chains can make succinimide formation less favorable.46
Bone marrow amyloid: a comprehensive analysis of 1,469 samples, including amyloid type, clinical features, and morphologic distribution
Published in Amyloid, 2022
April Chiu, Surendra Dasari, Paul J. Kurtin, Jason D. Theis, Julie A. Vrana, Angela Dispenzieri, Karen L. Rech, Linda N. Dao, Matthew T. Howard, Martha Grogan, Ellen D. McPhail
Amyloidosis represents a heterogeneous group of disorders characterised by extracellular deposition of abnormal protein fibrils in cross beta sheets. To date thirty-six human tissue-specific amyloid proteins have been recognized [6], and accurate identification of the amyloid type is paramount for optimal patient management. Since 2008 we have performed tandem mass spectrometry (MS/MS) to type amyloid specimens by shotgun proteomics, which provides an efficient and unbiased method to identify all amyloid types in a single assay [7,33]. The bone marrow is one of the five anatomic sites most commonly analysed in our laboratory, along with heart, kidney, GI tract, and fat aspirate/biopsy [7]. One of the most common indications for bone marrow biopsy in these patients is clinical suspicion of cardiac amyloidosis in the setting of a concomitant monoclonal protein. This scenario requires histologic confirmation of amyloidosis, as cardiac scintigraphy, a non-invasive technique for diagnosing ATTR cardiac amyloidosis, lacks specificity in this setting [25,32]. One of the preferred initial biopsy sites is bone marrow, as it is readily accessible and the yield is high overall. Although these patients are often assumed to have AL amyloidosis, previous studies have identified bone marrow amyloid in 30% of ATTRwt patients [13]. It therefore should not be surprising that although AL was common, over 10% of our patients with cardiac amyloid and a concomitant M-spike had bone marrow involvement by ATTR amyloid (Figure 1(B)).
Envelope proteins as antiviral drug target
Published in Journal of Drug Targeting, 2020
Jyoti Verma, Naidu Subbarao, Maitreyi S. Rajala
Envelope glycoproteins of Flaviviruses and Alphaviruses are class II fusion proteins. Unlike class I fusion proteins, class II proteins form a dimer in their pre-fusion conformation. These proteins primarily consist of beta sheets forming three structural domains termed I, II and III [25]. Domain I is the central domain having a beta barrel form with two long insertions connecting adjacent beta strands forming elongated domain II at one end. Domain II consists of highly conserved fusion loop. At the C-terminal of domain I, a linker region extends to connect domain III which has an immunoglobulin superfamily fold and a stem region connecting the protein to the transmembrane anchor [26]. Class II fusion proteins undergo a re-arrangement converting from a pre-fusion dimer (homo- or hetero-) to a homotrimer conformation. Domain I and II form the core of the homotrimer with three fusion loops at the tip of the trimer and domain III folds back against the core trimer moving towards the fusion loop. This trimeric hairpin is analogous to the six-helix bundle in the class I proteins [27].