Cell surface receptors recognition

Chai, Q., Arndt, J.W., Dong, M., Tepp, W.H., Johnson, E.A., Chapman, E.R., and Stevens, R.C. 2006. Structural basis of cell surface receptor recognition by botulinum neurotoxin B. Nature 444 1090-1100. 

The cell surface additionally displays receptors responsible for cell-cell recognition [28]. Members of this class of receptors are selectins [29] that recognize specific carbohydrates from other cells in the presence of calcium. Other cell surface receptors belong to the immunoglobulin superfamily (IgSF) [30] that promote calcium-independent cell-cell adhesion. The third important class are the calcium-dependent cell adhesion molecules, the cadherins [31], which form dimers with cadherin molecules presented on the surfaces of other cells and hence promote aggregation of similar cell types. 

Newel PC, Aggregation and cell surface receptors in cellular slime molds. In Cuatrecasas P, Greaves ME (eds.). Receptors and Recognition, pp. 1—58, 1977. 

Studies on molecular recognition by artificial receptors are thus one of the most important approaches to such characterization in relation to supramolecular chemistry [4]. Functional simulation of intracellular receptors in aqueous media has been actively carried out with attention to various noncovalent host-guest interactions, such as hydrophobic, electrostatic, hydrogen-bonding, charge-transfer, and van der Waals modes [5-10]. On the other hand, molecular recognition by artificial cell-surface receptors embedded in supramolecular assemblies has been scarcely studied up to the present time, except for channel-linked receptors [11-13]. 

We have already reported that synthetic peptide lipids, having ot-amino acid residuefs) interposed between a polar head moiety and a hydrophobic doublechain segment, can be used as models for functional simulation of biomembranes [23]. On this ground, we are to clarify molecular recognition specificity by supramolecular assemblies formed in combination of the macrocyclic receptors with the peptide lipid as artificial cell-surface receptors. 

The steroid cyclophane also provides a sizable and well-desolvated hydro-phobic cavity in aqueous media in a manner as observed for the octopus cyclophane. The molecular recognition ability of the steroid cyclophane is inferior to that of the octopus cyclophane in aqueous solution due to the structural rigidity of steroid segments of the former host. When the steroid cyclophane is embedded in the bilayer membrane to form a hybrid assembly, however, the steroid cyclophane becomes superior to the octopus cyclophane with respect to functions as an artificial cell-surface receptor, performing marked guest discrimination. 

The cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

Apolipoproteins The apolipoproteins associated with lipoprotein particles have a number of diverse functions, such as providing recognition sites for cell-surface receptors, and serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. Some of the apolipoproteins are required as essential structural components of the particles and cannot be removed (in fact, the particles cannot be produced without them), whereas others are transfered freely between lipoproteins. Apolipoproteins are divided by structure and function into five major classes, A through E, with most classes having subclasses, for example, apo A-l and apo C-ll. [Note Functions of all of the apolipoproteins are not yet known.]... 

Here are two of many known examples of specific cell-cell adhesion. The species-specific reaggregation of dissociated cells of marine sponges (Chapter 1) depends upon a 20-kDa proteoglycan of unique structure209-211 together with a cell surface receptor protein and calcium ions. The recognition of egg cell surfaces by sperm212-214 is species... 

Recognition domains often function transiently. For example, SH2 domains are often found in proteins that interact with phosphotyrosyl groups of "activated" cell surface receptors. The receptors become activated... 

X-ray crystallography of the 65-kDa form reveal a three-domain structure. The central domain varies among different strains and is probably involved in recognition and in binding to cell surface receptors.e h The toxin binds to a receptor, apparently an aminopeptidase N, after which the toxin is rapidly inserted into the membrane forming a 1- to 2-nm diameter pore. This leads to cell death.)... 

Several laboratories have studied the assimilation of specific lysosomal enzymes using as model systems skin fibroblasts deficient in the enzyme under study. The underlying mechanism for the translocation of lysosomal enzymes was hypothesized to involve binding of carbohydrate-containing recognition markers to specific cell surface receptors (1 5). In support of this hypothesis Hickman, Shapiro, and Neufeld (16J found that treatment of N-acetyl-B-hexosaminidase with periodate under conditions that dTd not affect enzymatic activity prevented the efficient assimilation of this enzyme by Sandhoff fibroblasts. Additionally, Kresse and von Figura (1 7) found that treatment of f -acetyl-a-hexosaminidase with B-galactosidase reduced the assimilation of this enzyme by San-filippo B fibroblasts. 

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