Protein folding membrane-embedded proteins

Soluble proteins exhibit hundreds of distinct localized folded structures, or motifs (see Figure 3-6). In comparison, the repertoire of folded structures in Integral membrane proteins Is quite limited, with the hydrophobic a helix predominating. Integral proteins containing membrane-spanning ct-hellcal domains are embedded in membranes by hydrophobic Interactions with specific lipids and probably also by Ionic Interactions with the polar head groups of the phospholipids. 

The inner membrane is highly folded to create a large surface area. The folded membranes are known as cristae. The inner mitochondrial membrane is almost completely impermeable to most substances. For this reason it has many transport proteins to bring particular fuel molecules into the matrix space. Also embedded within the inner mitochondrial membrane are the protein electron carriers of the electron transport system and ATP synthase. ATP synthase is a large complex of many proteins that catalyzes the s)mthesis of ATP. 

Proteins whose folding must occur in the membrane, such as integral membrane proteins, need to be translated within the organelle so they can dock with the membrane in the folding process. They often have to be embedded with a surface on the inner face of the organelle membrane. These proteins cannot be synthesized in the cytoplasm and then exported to the organelle, as the folding environment of the cytoplasm would probably produce an incorrect fold. 

These genomes code for proteins that, during translation and folding, become embedded into the organelle membrane. Most of the proteins that are required by the organelle are of nuclear origin, and they are imported... 

Integral membrane proteins. Membrane proteins are hard to crystallize178 and precise structures are known for only a few of them.179-181 A large fraction of all of the integral membrane proteins contain one or more membrane-spanning helices with loops of peptide chain between them. Folded domains in the cytoplasm or on the external membrane surface may also be present. The best-known structure of a transmembrane protein is that of the 248-residue bacteriorhodopsin. It consists of seven helical segments that span the plasma membrane (Fig. 23-45) and serves as a light-activated proton pump. Other proteins with similar structures act as hormone receptors in eukaryotic membranes. A seven-helix protein embedded in a membrane is depicted in Fig. 8-5 and also, in more detail, in Fig. 11-6. 

The Fenna-Matthews-Olson (FMO) protein is an unusual, water-soluble chlorophyll protein found only in green sulfur bacteria. [18] It is believed to be located between the chlorosome and the cytoplasmatic membrane and functions as an excitation transfer link between the chlorosome and the reaction center. Each subunit contains 7 BChl a molecules embedded in a primarily /3 sheet structured protein. The protein has a trimeric quaternary structure, with a three-fold axis of symmetry in the center of the complex. [55] The green nonsulfur bacteria do not contain the FMO protein. In these organisms the chlorosome transfers energy directly to the integral membrane core antenna B808-865, and then to the reaction center. 

Connectivity has a central role in biochemistry and biology, and one imagines that the percolation model, with its focus on connectivity, should have wide application. Percolative behavior is to be expected for the coordinate functioning of systems of proteins in metabolic pathways, for functional interactions between proteins embedded in a membrane, for the interactions between domains in the folding of a polypeptide, or for the onset of function in anhydrobiotic organisms, seeds, and spores. 

This disorder is caused by defects in one of the subunits leading to a molecule which does not integrate into the plasma membrane directly or which does not fold correctly and which is therefore degraded. Mutations leading to BSS have been detected in all of the subunits with the exception of GPV. Although this may merely mean that mutations in GPV have simply not been detected, another possible interpretation is, that, while the expression of the other subunits are necessary for the expression of GPV, GPV expression may not be necessary for the expression of the rest of the complex. The types of mutations that have been detected so fer M into a number of categories. Several mutations in GPIba are the type that lead to a frameshift and to a nonsense or stop codon before the transmembrane domain is translated, with the result that this subunit does not become embedded in the membrane and is expressed as a soluble protein (87, 88). Recently,... 

Each mitochondrion (plural mitochondria) is bounded by two membranes (Figure 2.24a). The smooth outer membrane is relatively porous, because it is permeable to most molecules with masses less than 10,000 D. The inner membrane, which is impermeable to ions and a variety of organic molecules, projects inward into folds that are called cristae (singular crista). Embedded in this membrane are structures composed of molecular complexes and called respiratory assemblies (described in Chapter 10) that are responsible for the synthesis of ATP. Also present are a series of proteins that are responsible for the transport of specific molecules and ions. 

Bacteriorhodopsin is an integral bacterial membrane protein. As seen in Figure 10.15, the linear polypeptide chain of bacteriorhodopsin folds back and forth several times in the membrane to provide a channel through which protons move. Figure 10.16 shows that a plot of the hydrophobic tendency of amino acids in the protein parallels the regions embedded in the membrane. Thus, hydrophobic regions of the protein are embedded in the protein and hydrophilic regions are at the surfaces. 

Proteins are originally synthesized inside ribosomes in the cytoplasm or ribosomes inside the endoplasmic reticulum (ER). The latter synthesize proteins intended to be embedded in the cell membrane (Conn and Jamovick, 2005). When released from the ribosomes, the protein backbone first folds in groups of four or more amino acids to limit interference from bulky or charge-bearing... 

Holm et al. have referred to metalloproteins as elaborated inorganic complexes, and it is computationally and conceptually useful to consider the immediate environment of a transition metal in a protein active site as a coordination complex surrounded by an unusual solventlike environment provided by the folded polypeptide of the protein. In many cases, redox active metal binding sites are sufficiently embedded in the protein matrix such that the actual solvent (water and/or lipid membranes) may have little impact on the redox thermochemistry of the site. Specific features of the active site beyond the first coordination shell (e.g., hydrogen bonds, charged peptide side chains) can have a significant impact on the redox properties of the site. Spectroscopic probes based on the properties of the metal reporter can then provide detailed information about the bonding and electronic structure of the redox active site. Thus, rather spatially limited theoretical calculations on redox active metal sites can be used to complement and interpret experimental data. 

The inner membrane encloses the matrix or stroma, which is a contractile network of structural proteins embedded in an aqueous phase. The inner membrane also shows characteristic folds, known as cristae, which extend into the matrix. In some cases these... 

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