Promiscuous binding

TM) GPCRs, and the identification of these two molecules facilitated the discovery of many of the other chemokine receptors. The identification of the two IL8 receptors was followed, shortly after, by the cloning of a receptor for CC chemokines. This receptor was initially called CC-CKR1 (now CCR1) and was shown to promiscuously bind a number of members of the CC chemokine family (6). Subsequent to the identification of these three chemokine receptors, two principal methods have been used to clone the cDNAs for the other currently identified receptors ... 

FIGURE 2 7-2 Neurotrophin receptors. Neurotrophin family members bind specifically to cognate Trk receptors. The low affinity neurotrophin receptor, p75, promiscuously binds all neurotrophins. BDNF, brain-derived neurotrophic factor NGF, nerve growth factor NT, neurotrophin. 

Panina-Bordignon P, et al. Universally immunogenic T cell epitopes promiscuous binding to human MHC class II and promiscuous recognition by T cells. Eur J Immunol 1989 19 2237. 

Nakshatri, H., and Chambon, P. (1994). The Directly Repeated RG(G/T)TGA Motifs of the Rat and Mouse Cellular Retinol-Binding Protein II Genes Are Promiscuous Binding Sites for RAR, RXR, HNF-4, and ARP-1 Homo- and Heterodimers./. 

Proteins such as cytochromes P450 and the hERG channel accommodate structurally diverse drugs to the extent that the promiscuous binding of drugs to these proteins is a major problem in drug development. Recently highly selective inhibitors have been developed [34,35],... 

Kell DB, Dobson PD, Bilsland E, Oliver SG (2013) The promiscuous binding of pharmaceutical drugs and their transporter-mediated uptake into cells what we (need to) know and how we can do so. Drug Discov Today 18(5-6) 218-239... 

Due to its promiscuous binding, ricin becomes localised to all types of membrane invaginations (Sandvig and van Deurs, 1996) and as such, is a valuable tool in the study of different endo-cytic mechanisms (Sandvig and van Deurs, 2000 Iversen et al, 2001) (Figure 1). Ricin endocy-tosis via clathrin-coated pits has been demonstrated (van Deurs et al, 1985). There is also evidence of clathrin-independent mechanisms of toxin uptake. For example, Hep-2 cells, in which coated pit formation has been blocked by hypotonic shock and potassium ion depletion, remain sensitive to ricin (Moya et al, 1985). 

Evidence for both models exists, and while the action of mtHsp70 remains controversial, most evidence indicates that BiP acts as a ratchet. Using purified proteins in surface plasmon resonance assays, it was shown that the Sec63p J-domain could bind and activate BiP to bind peptide substrates in its immediate vicinity in the presence of ATP. In this manner, BiP could bind to a wide range of substrates, including some that it would not normally bind to on its own (Misselwitz et al, 1998). Such promiscuous binding would be favorable to preprotein translocation in... 

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