Proteins circular

Camarero, J. A., Fushman, D., Cowburn, D., and Muir, T. W. (2001) Peptide chemical ligation inside living cells in vivo generation of a circular protein domain. Bioorg. Med. Chem. 9, 2479-2484. 

Nucleotide-excision repair involves PCNA, DNA polymerase epsilon, and several accessory proteins, such as RF-C (replication factor C), RP-A (replication protein A), and Lig I (DNA ligase I). It could be that these proteins form an aggregate DNA repair machine. PCNA is a hollow circular protein that encircles DNA. PCNA binds and activates many proteins involved in DNA repair. Mismatch repair is less well characterized, but involves DNA polymerase delta. 

In this complex situation the histological diagnosis of chronic CsA nephrotoxicity should rely in the finding of the typical afferent arteriolar lesion with nodular focal or circular protein deposits in the tunica media [242]. However, when renal biopsies are performed tardily, after months or years of continuous renal injury, the morphological picture may be "dirty" and very difficult to characterize. Moreover, vascular or chronic rejection may coexist with CsA chronic nephrotoxicity. Finally, as previously pointed, recent studies showed that CsA-induced fibrosis can occur without afferent arteriole injury and that CsA-induced af-... 

Conceptually, the amino and carboxyl termini of a polypeptide chain are flexible and amendable to form a peptide bond. The formation of the terminally linked peptide bond yields circular (cyclic) proteins with circular backbones. Cyclic peptides such as cyclosporin are known. These peptides tend to be less than 12 amino acids in size, contain modifled amino acids and are generally metabolic products. Whereas circular proteins are 14-70 amino acids in size, true gene products (encoded by DNA) with well-defined 3D structures. They occur in microorganisms, plants and animals, as products for an enhanced stability or involvement in host defense (Trabi and Craik, 2002). Several naturally occurring circular proteins are listed in Table 5.10. CyBase (http //research.imb.uq.edu.au/ cybase) is the curated database for cyclic proteins. 

TABLE 5.10 Some naturally occurring circular proteins... 

Felizmenio-Quimio ME, Daly NL, Craik DJ (2001) Circular proteins in plants solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis. J Mol Biol 276 22875-22882... 

Magnetic circular dicliroism (MCD) is independent of, and thus complementary to, the natural CD associated with chirality of nuclear stmcture or solvation. Closely related to the Zeeman effect, MCD is most often associated with orbital and spin degeneracies in cliromophores. Chemical applications are thus typically found in systems where a chromophore of high symmetry is present metal complexes, poriihyrins and other aromatics, and haem proteins are... 

Ihe rule-based approach to protein structure prediction is obviously very reliant on th quality of the initial secondary structure prediction, which may not be particularly accurate The method tends to work best if it is known to which structural class the protein belongs this can sometimes be deduced from experimental techniques such as circular dichroism... 

Measuring Protein Sta.bihty, Protein stabihty is usually measured quantitatively as the difference in free energy between the folded and unfolded states of the protein. These states are most commonly measured using spectroscopic techniques, such as circular dichroic spectroscopy, fluorescence (generally tryptophan fluorescence) spectroscopy, nmr spectroscopy, and absorbance spectroscopy (10). For most monomeric proteins, the two-state model of protein folding can be invoked. This model states that under equihbrium conditions, the vast majority of the protein molecules in a solution exist in either the folded (native) or unfolded (denatured) state. Any kinetic intermediates that might exist on the pathway between folded and unfolded states do not accumulate to any significant extent under equihbrium conditions (39). In other words, under any set of solution conditions, at equihbrium the entire population of protein molecules can be accounted for by the mole fraction of denatured protein, and the mole fraction of native protein,, ie. 

A gene encoding this sequence was synthesized and the corresponding protein, called Janus, was expressed, purified, and characterized. The atomic structure of this protein has not been determined at the time of writing but circular dichroic and NMR spectra show very clear differences from B1 and equally clear similarities to Rop. The protein is a dimer in solution like Rop and thermodynamic data indicate that it is a stably folded protein and not a molten globule fold like several other designed proteins. 

An aerial view of the European Synchrotron Radiation Facility at Grenoble, France, an advanced source of synchrotron x-ray radiation for use in the study of protein structure, as well as for use in the physical and material sciences. The synchrotron radiation is produced in the circular building in the lower left of the photograph. (Courtesy of ESRF.)... 

The space inside the inner mitochondrial membrane is called the matrix, and it contains most of the enzymes of the TCA cycle and fatty acid oxidation. (An important exception, succinate dehydrogenase of the TCA cycle, is located in the inner membrane itself.) In addition, mitochondria contain circular DNA molecules, along with ribosomes and the enzymes required to synthesize proteins coded within the mitochondrial genome. Although some of the mitochondrial proteins are made this way, most are encoded by nuclear DNA and synthesized by cytosolic ribosomes. 

This concept is demonstrated schematically in Figure 1.11. It can be seen that the initial bias in a system of proteins containing two conformations (square and spherical) lies far toward the square conformation. When a ligand (filled circles) enters the system and selectively binds to the circular conformations, this binding process removes the circles driving the backward reaction from circles back to squares. In the absence of this backward pressure, more square conformations flow into the circular state to fill the gap. Overall, there is an enrichment of the circular conformations when unbound and ligand-bound circular conformations are totaled. 

Mitochondria are unique organelles in man and higher animals in that they contain their own genome. Mitochondrial DNA (mtDNA) in humans is a small (16.5 kb), circular genome that encodes only 13 proteins, 22 transfer RNA (tRNA), and 2 ribosomal RNA (rRNA) molecules. mtDNA is inherited only from the mother and is present in multiple copies within one mitochondrion. 

---