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Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
In humans, the immunoglobulins or antibodies are divided into five distinct classes (IgG, IgM, IgA, IgE, and IgD), that share similar structures composed of immunoglobulin domains, but are different in the amino acid sequences in the heavy chains (57–59). In IgG, IgA, and IgD, the Fc and Fab are linked by a flexible hinge region that has no defined secondary structure. In IgM and IgE, this flexible linker is replaced by a more rigid Ig domain. The hinge region can contain N- and O-linked glycans (57).
Pathways of Cell Recruitment to Mucosal Surfaces
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Although human and murine MAdCAM-1 sequences are quite divergent, sequence comparisons demonstrate that the first two (N-terminal) Ig-like domains, at 57% identity (compared to 39% for the entire protein), are the most highly conserved regions of these receptors. The 2 Ig loops display several features conserved with murine MAdCAM-1, including 1.) double cysteine residues, separated by 3 amino acids in the first Ig domain; 2.) an identical nine amino acid stretch in Ig domain 1, containing the sequence LDTSL, which aligns with a consensus motif for integrin/IG family member interactions (Fig. 3) (116,118–120); and 3.) a uncharacteristically large second immunoglobulin domain, with approximately 70 amino acids between cysteine residues. This is a novel feature in comparison to other Ig-like adhesion receptors, which usually have 40 to 50 residues between the cysteines in each domain (121,122). Interestingly, the homology to IgA observed in murine MAdCAM-1 is not retained in human MAdCAM-1. The function of the IgA-like domain in murine MAdCAM-1 has yet to be determined.
Immunoglobulins
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The fundamental architectural theme of the immunoglobulin molecule is a four chain structure containing two identical light (L) chains of Mr 23 kDa, and two identical heavy (H) chains of Mr 55 kDa (Figure 4–7). The H and L polypeptides assume characteristic secondary and tertiary structures forming the immunoglobulin domains (Figure 4–8). Light chains have two domains; heavy chains have four or five. The domain structures formed by an individual H or L chain, and the complete four chain unit, H2L2, are maintained by covalent and non-covalent interactions. A domain consists of approximately 110 amino acids organized into two regions of β-pleated sheet held apposed (sandwich fashion) by a disulfide bridge. The four chain unit is also usually stabilized by disulfide bonds between H and L chains, and between the two H chains (Figure 4–7). Non-covalent interactions stabilizing antibody structure are hydrogen bonds, electrostatic forces, van der Waal’s forces, and hydrophobic interactions (see below).
Novel ligands and modulators of triggering receptor expressed on myeloid cells receptor family: 2015-2020 updates
Published in Expert Opinion on Therapeutic Patents, 2021
Harbinder Singh, Vikrant Rai, Sunil K. Nooti, Devendra K. Agrawal
A family of cell surface receptors, ‘TREM’ or ‘triggering receptor expressed on myeloid cells,’ are group of activating receptors that are particularly expressed on myeloid cells, such as monocytes, macrophages, neutrophils, mast cells, and dendritic cells (DCs). TREMs are primarily transmembrane glycoproteins having an immunoglobulin (Ig)-type fold in their extracellular domain, thus belonging to the Ig-superfamily. These receptors have been found to be important pathological hallmarks in various inflammatory disorders of infectious as well as noninfectious disease conditions such as myocardial infarction, atherosclerosis, sepsis, gout, renal fibrosis, pancreatitis, cancer, etc. [1]. Structurally, these receptors contain three units: (i) extracellular immunoglobulin domain, (ii) a transmembrane region, and (iii) short cytoplasmic domain [2] (Figure 1). In their cytoplasmic domain, there are no signaling motifs, therefore, transmembrane domains associate with the immunoreceptor tyrosine-based activation motif (ITAM)-containing molecule DAP12 (DNAX activation protein of molecular weight 12 kDa) to express their functions [3].
Anticalin® proteins: from bench to bedside
Published in Expert Opinion on Biological Therapy, 2021
Friedrich-Christian Deuschle, Elena Ilyukhina, Arne Skerra
Due to the complex composition of in total 12 immunoglobulin domains (as for IgG1), with numerous intra- and interchain disulfide bonds and obligatory glycosylation in the Fc region, the manufacturing of mAbs requires time-consuming and costly mammalian expression systems. Their considerable molecular size of ~150 kDa hampers tissue penetration while leading – in combination with the FcRn-mediated endosomal recycling process – to a very long plasma half-life of several days to even weeks. Accordingly, mAbs are only suited to a limited extent for treatments that require a fast adjustment of the circulating drug concentration [4]. Likewise, mAbs are not ideal for the expanding field of in vivo diagnostics, including modern theranostic strategies in nuclear medicine, since molecular imaging requires high specificity and good tissue penetration combined with fast blood clearance [5]. Furthermore, the immunological effector functions – mediated by the Fc portion of the mAb [6] – although potentially beneficial in oncology, are superfluous or even disadvantageous for many therapeutic applications, especially if anta-gonistic blocking of target receptors, cytokines or growth factors constitutes the mode of action.
Quantification of natural abundance NMR data differentiates the solution behavior of monoclonal antibodies and their fragments
Published in mAbs, 2021
David Ban, Cory T. Rice, Mark A. McCoy
We acquired natural abundance 2D [1H, 13C]-HMQC datasets for 20 different molecules that span four different Ab(L/F) classes with MWs between 12 and 150 kDa (Table S1). Figure 1 displays examples of 2D NMR datasets from the four different classes of Ab(L/F)s evaluated here. The set included individual VHH domains (Figure 1a; red), multivalent or tethered VHH domains (Figure 1b; blue), antigen-binding fragment (Fab; Figure 1c; green) and full-length mAb (Figure 1d; cyan). From the 2D NMR datasets, only qualitative differences between the classes of molecules are evident in Figure 1a-d. The classes were specifically chosen to enable construction of a set that could distinguish features based on their modular construction. As a rough approximation, the selected classes are composed of single to multiples of small immunoglobulin domain(s) that are folded or tethered together.