Translocation coordinate

Genetic mutations also have been reported for mitochondrial proteins encoded by nuclear DNA. Most of the estimated 1,000 proteins required for oxidative phosphorylation are encoded by nuclear DNA, whereas mtDNA encodes only 13 subunits of the oxidative phosphorylation complexes (including ATP synthase). Nuclear DNA encodes the additional 70 or more subunits of the oxidative phosphorylation complexes, as well as adenine nucleotide translocase (ANT) and other anion translocators. Coordinate regulation of expression of nuclear and mtDNA, import of proteins into the mitochondria, assembly of the complexes, and regulation of mitochondrial fission are nuclear encoded. 

Fig. 15 (a) DNA translocation through a protein pore in a-hemolysin. When the DNA enters the pore, the ionic current is blocked. This current blockage is used to detect the residence time of DNA bases in the pore [67]. (b) Chain translocation through a nanopore. The instantaneous translocation coordinate is s(t) and the bead velocity in the pore is v(t). The driving force is due to a chemical potential gradient within the pore, f = (ni — Adapted from [68]. Reproduced... 

Fig. 16 (a) The probability distribution of translocation coordinate t) at five different time moments (symbols) along with Gaussian fits (lines) with variance A. (b) Increase of the variance A(/) with elapsed time t, indicating a crossover fi-om short-time subdiffusive behavior ex to late time nearly normal diffusive behavior oc. Reprinted with permission from [87]... 

Fig. 17 (a) Dynamic response of a driven polymer translocation upon switching the pulling force/. At time t the tension force has passed the N(f) monomer and is at distance X t) from the membrane while M i) monomers have already moved into the trans side of the separating membrane. The chain portion to the right of X(t) is moving with mean velocity v(t). (b) First and second moments of the translocation coordinate (s) and (s ), and the variance (As(t) ) = (s ) - (s) for a polymer chain with length JV = 100 and driving force / = 5.0. Reprinted with permission from [89]... 

The above analytical results are derived only for the simple model of the inside of a pore, with the drift force being a constant independent of the translocation coordinate m. We consider next several examples of more complex situations. 

LDL (apo B-lOO, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-lOO binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase, and, therefore, cholesterol synthesis stimulates ACAT activ-... 

The hemopexin heme transport system thus acts as an early warning system for cells by activating signaling pathways (including the N-terminal c-Jun kinase, kinases to release RbIA/NFkB family members for nuclear translocation) and transcription of the HO-1 and MT-1 genes. The details of this aspect of hemopexin function with redox-active copper as an initial event in the coordinated induction of HO-1 and MT-1 by heme-hemopexin have recently been reviewed (89) and are not presented in detail here. 

The R-Smad proteins interact with type I receptor and co-regulatory Smad (co-Smad) proteins in the signal cascade by virtue of conserved MH1 and MH2 domains at their N- and C-termini, which are separated by a variable, non-conserved region. These domains possess DNA binding and transcriptional activation functions, respectively. The inactive MH1 domain interacts with the MH2 domain in an auto-inhibitory manner. However, once C-terminal phosphorylation by the type I receptor occurs, this inhibitory association is alleviated and the R-Smad is then able to interact with its appropriate co-Smad. The phosphorylated R-Smad/co-Smad complex is capable of translocation to the cell nucleus where, in coordination with nuclear factors, it is able to exert its transcriptional activation function. 

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