Protein interactions with ligands

Formulating proposed mechanisms of protein action requires investigating how proteins interact with ligands of all kinds, including other proteins. Molecular modeling programs allow the user to display and manipulate several... 

A protein interacts with a metabolite. The metabolite is dins a ligand which binds. specifically to this protein... 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Successful affinity chromatography requires that the protein interact with an immobilized ligand tightly enough to be captured from solution,... 

The general types of protein-protein interactions that occur in cells include receptor-ligand, enzyme-substrate, multimeric complex formations, structural scaffolds, and chaperones. However, proteins interact with more targets than just other proteins. Protein interactions can include protein-protein or protein-peptide, protein-DNA/RNA or protein-nucleic acid, protein-glycan or protein-carbohydrate, protein-lipid or protein-membrane, and protein-small molecule or protein-ligand. It is likely that every molecule within a cell has some kind of specific interaction with a protein. 

Fig. 4.4. The principle of signal transduction by nuclear receptors. Nuclear receptors are ligand-controlled transcription factors that bind cognate DNA sequences, or hormone responsive elements (HRE). The hormone acts as a regulating ligand. Most nuclear receptors bind their cognate HREs, which tend to be symmetrically organized, as homo- or heterodimers. The DNA-bound, activated receptor stimulates transcription initiation via direct or indirect protein-protein interactions with the transcription initiation complex. The arrows demonstrate the different possible configurations of the HRE (see also 4.6). H hormone Hsp heat shock protein.

F1GURE 5-22 Structure of a human class I MHC protein, (a) This model is derived in part from the known structure of the extracellular portion of the protein (PDB ID 1 DDH). The a chain of MHC is shown in gray the small /3 chain is blue the disulfide bonds are yellow. A bound ligand, a peptide derived from HIV, is shown in red. (b) Top view of the protein, showing a surface contour image of the site where peptides are bound and displayed. The HIV peptide (red) occupies the site. This part of the class I MHC protein interacts with T-cell receptors. 

Computer simulations are regularly performed of the energetics of protein structure and their interactions with ligands using potential energy functions for the forces described so far. The energy functions are of necessity simplifications, but they are calibrated on experimental data. A minimalist model uses equation 11.3.15... 

Fig. 8. Schematic of a hypothetical protein interacting with a crosslinked agarose gel containing certain bonding sites. The bonding sites on the gel are considered to be immobilized ligands...

Cell map proteomics reveals the static proteome of a whole organism, tissue, cell or organelle, while expression proteomics investigates changes in a proteome to cellular cues (Godovac-Zimmermann and Brown, 2001). Functional and structural proteomics refers to the investigation of individual proteins such as interactions with ligands. 

F. Are Unique Conformational Changes in Receptors Elicited by Interactions with Ligands Resulting in Varied G Protein Interactions... 

GPCR interactions with ligand and G protein are represented by the ternary complex formalism (Fig. 2A Christopoulos and Kenakin, 2002 De Lean et al, 1980 Sam am a et al, 1993). The quantitative analysis of the soluble assembly system formally requires inclusion of soluble G protein due to the use of a crude receptor preparation. These soluble G proteins compete with the G protein attached to the G-beads for the solubilized receptor as shown in Fig. 2C (Simons et al, 2003, 2004). Experimental values from G-beads (Fig. 3) were fitted with the calculations of bead-bound receptors (RG k..i< + ARG k. i< ) based on this model, which includes soluble G proteins. Simulations were made by Mathematica , numerically solving the series of... 

Fig. 3. Two-dimensional analysis of PDZ proteins interacting with the 5-HT2A and the 5-HT2C receptors C-termini. (A) Proteins from mice brain that bind to the C-terminus of the last 14 residues of the receptors were separated on 2D gels and stained with silver. Proteins that interact specifically (directly or indirectly) with the PDZ ligand of the receptor (arrows) were detected comparing protein patterns obtained with the native peptides (see Fig. 1) and mutant peptides in which the last residue was replaced by alanine. The position of one protein retained in a PDZ-independent manner by the 5-HT2A receptor C-terminus is also indicated (arrowhead). (B) Molecular determinants in the C-terminus of 5-HT2A receptor involved in its preferential interaction with CIPP.

Molecular recognition Double-helical DNA is able to interact with ligands, e.g. DNA-binding proteins, often in a very site-selective way, providing the basis for the modulation of electron transport. 

A protein tail, which is the same in all library members, is fused to the C-terminus of the ribosome display construct and serves as a spacer. This spacer has two main functions. First, it tethers the synthesized protein to the ribosome. Second, it keeps the structured part of the protein outside the ribosome and allows its folding and interaction with ligands, without clashing with the ribosomal tunnel. The ribosomal tunnel covers between 20 and 30 C-terminal amino acids of the nascent polypeptide chain during protein synthesis and can therefore prevent the folding of the protein (Malkin and Rich, 1967 Smith et al., 1978). 

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