Protein disposition

Figure 13.6. Schematic representation of size-dependent protein disposition mechanisms. Depending on molecular weight, a protein or peptide predominantly undergoes selective Inactivation.

Wroblewski, V.J. (1991) Mechanism of deiodination of 1251-human growth hormone in vivo. Relevance to the study of protein disposition. Biochem. 

Figure 46-5 shows a variety of ways in which proteins are distributed in the plasma membrane, in particular, the amino terminals of certain proteins (eg, the LDL receptor) can be seen to be on the extracytoplasmic face, whereas for other proteins (eg, the asialoglycoprotein receptor) the carboxyl terminals are on this face. To explain these dispositions, one must consider the initial biosynthetic events at the ER membrane. The LDL receptor enters the ER membrane in a manner analogous to a secretory protein (Figure 46-4) it partly traverses... 

Topogenic sequences (eg, signal [amino terminal or internal] and stop-transfer) are important in determining the insertion and disposition of proteins in membranes. 

It should be noted that there are a variety of ion channels (Chapter 41) in most cells, for Na, K, Ca, etc. Many of them have been cloned in recent years and their dispositions in their respective membranes worked out (number of times each one crosses its membrane, location of the actual ion transport site in the protein, etc). They can be classified as indicated in Table 49-4. Cardiac muscle is rich in ion channels, and they are also... 

The major proteins (which include spectrin, ankyrin, the anion exchange protein, actin, and band 4.1) have been studied intensively, and the principal features of their disposition (eg, integral or peripheral), structure, and function have been established. 

Figure 18.5 Schematic representation of possible cleavage sites of APP by a, and y-secretase and the production of j5-amyloid protein. (I) This shows the disposition of APP molecules in 695, 751 and 770 amino-acid chain lengths. Much of it is extracellular. The /1-amyloid (A/I4) sequence is partly extracellular and partly in the membrane. (II) An enlargement of the /1-amyloid sequence. (Ill) Normal cleavage of APP by a-secretase occurs in the centre of A/I4 sequence to release the extracellular APP while the remaining membrane and intracellular chain is broken down by y-secretase to give two short proteins that are quickly broken down. (IV) In Alzheimer s disease ji rather than a-secretase activity splits off the extracellular APP to leave the full AP4 sequence remaining attached to the residual membrane and intracellular chain. 42/43 amino acid )S-amyloid sequence is then split off by y-secretase activity...

The enzymes are protein molecules having globular structure, as a rule. The molecular masses of the different enzymes have values between ten thousands and hundred thousands. The enzyme s active site, which, as a rule, consists of a nonproteinic organic compound containing metal ions of variable valency (iron, copper, molybdenum, etc.) is linked to the protein globule by covalent or hydrogen bonds. The catalytic action of the enzymes is due to electron transfer from these ions to the substrate. The protein part of the enzyme secures a suitable disposition of the substrate relative to the active site and is responsible for the high selectivity of catalytic action. 

P2j Z = 2 DX = 1.43 R = 0.067 for 1269 intensities. The uracil residue is in the anti (63.4°) disposition. The conformation of the D-ribosyl group is 2T3 (176.8°, 37.5°). The orientation about the exocyclic, C-4 -C-5 bond is t (—174.2°). The phenyl and uracil ringsofthe same molecule lie in almost parallel planes, 120 pm apart. The phenyl group is disordered. The uracil ring is sandwiched by the phenyl rings, and vice versa. The 0-1 and N-a atoms of the peptide backbone are hydrogen-bonded to 0-4 and N-3 of atranslationally related uracil to form cyclic dimers. Such interactions serve as models for nucleic acid-protein interactions. [Coordinate errors H(02 ) x should be —1574, instead of —1474 H(Na)2 z should be —145 instead of— 645.]... 

It is unfortunately the case that when we incubate apoferritin with a certain number of iron atoms (for example as ferrous ammonium sulfate), the product, after elimination of non-protein-bound iron, does not have a homogeneous distribution of iron molecules which were able to (i) take up iron rapidly through the three fold channels, (ii) quickly transfer it and form a diiron centre on a ferroxidase site, and (iii) to transfer the iron inward to a nucleation site, where (iv) it will begin to catalyse iron oxidation on the surface of the growing crystallite, will accumulate iron much more rapidly, and in much greater amounts than molecules in which steps (i), (ii) and (iii) are slower, for whatever reasons (perhaps most importantly subunit composition, and the disposition of subunits of the two types H and L, one with regard to the other). This polydispersity makes the analysis of the process of iron uptake extremely difficult. 

Nanoparticle surface modification is of tremendous importance to prevent nanoparticle aggregation prior to injection, decrease the toxicity, and increase the solubility and the biocompatibility in a living system [20]. Imaging studies in mice clearly show that QD surface coatings alter the disposition and pharmacokinetic properties of the nanoparticles. The key factors in surface modifications include the use of proper solvents and chemicals or biomolecules used for the attachment of the drug, targeting ligands, proteins, peptides, nucleic acids etc. for their site-specific biomedical applications. The functionalized or capped nanoparticles should be preferably dispersible in aqueous media. 

Another, but less well defined, class of molecules, some of whose members mediate adhesion interaction, is the four-transmembrane domain family, which shares similar hydropathy plots and may have similar dispositions with respect to the phospholipid bilayer, for example the myelin proteolipid proteins, the connexins of gap junctions, the ryanodine receptor and others. 

Reigner, B.G., J.F. Rigod, and T.N. Tozer. 1992b. Disposition, bioavailability, and serum protein binding of pentachlorophenol in B6C3F1 mouse. Pharmaceut. Res. 9 1053-1057. 

Kitteringham NR, Christie G, Coleman JW, et al. Drug-protein conjugates XII a study of the disposition, irreversible binding and immunogenicity of penicillin in the rat. Biochem Pharmacol 1987 36 601-608. 

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