Process precursor protein

The shell of all picomaviruses is built up from 60 copies each of four polypeptide chains, called VPl to VP4. These are translated from the viral RNA into a single polypeptide, which is posttranslationally processed by stepwise proteolysis involving viraily encoded enzymes. First, the polypeptide chain is cleaved into three proteins VPO (which is the precursor for VP2 and VP4), VPl and VP3. These proteins begin the assembly process. The last step of the processing cascade occurs during completion of the virion assembly the precursor protein VPO is cleaved into VP2 and VP4 by a mechanism that is probably autocatalytic but may also involve the viral RNA. VPl, VP2, and VP3 have molecular masses of around 30,000 daltons, whereas VP4 is small, being 7000 daltons, and is completely buried inside the virion. 

The human genome contains more than 90 different DUBs. Besides cleaving ubiquitin from distinct substrates, DUBs are also responsible for the recycling of free ubiquitin from ubiquitin chains and processing of ubiquitin- or ubiquitin like precursor proteins. Certain DUBs are also associated with the proteasome in order to detach ubiquitin chains before proteolysis. 

The efficient uptake of precursor proteins depends on their presentation in a translocation competent state. This is maintained in vivo by the specific interaction with a highly conserved group of proteins, the heat-shock or stress related proteins (hps70s). These act as molecular chaperones and interact with the proteins to maintain them in a correctly folded state, a process which is ATP dependent. 

The maturation of the precursor protein involves their proteolytic cleavage. There are two proteins important in this cleavage, so-called processing protease and protease enhancing peptide. These are now believed to be nonidentical subunits of the same enzyme. The structural requirements for recognition of the cleavage site are not fully understood and except for a positively charged residue at position (-2) there is no consensus sequence around this site. 

Elastin is a heavily crosslinked biopolymer that is formed in a process named elastogenesis. In this section, the role of elastin and the different steps of elastin production will be described, starting with transcription of the genetic code and processing of the primary transcript, followed by translation into the elastin precursor protein and its transport to the extracellular matrix. Finally, the crosslinking and fiber formation, which result in the transition from tropoelastin to elastin, are described. 

Affect proteolytic processing of precursor proteins to smaller products... 

Checler, F (1995) Processing of the /i-amyloid precursor protein and its regulation in Alzheimer s disease. J. Neurochem. 65 1431-1444. 

The HlV-1 protease is responsible for processing the protein precursors to the enzymes (integrase, protease and reverse transcriptase) and the structural proteins of the HIV-1 virus. Maw and Hall found that topological indices provide rehable QSAR models for the IC50 data of 32 HIV-1 protease inhibitors [29]. The best QSAR model, with r = 0.86, s=0.60 and q = 0.79, was obtained with the shape index Ka, the connechvity index the sum of HE-state indices for ah groups that act as... 

Figure 13.6. From left to right location of the P-amyloid region of amyloid precursor protein (APP) in relation to the neuronal membrane normal processing of APP inactivates P-amyloid abnormal processing of APP in Alzheimer s disease liberates intact P-amyloid.

Gandy, S. and Greengard, P. Processing of Alzheimer Ab-amloid precursor protein cell biology, regulation, and role in Alzheimer disease. Int. Rev. Neurobiol. 35 29-50, 1994. 

Alzheimer s disease, Parkinson s disease, Huntington s disease and amyotrophic lateral sclerosis (ALS) are four prominent fatal neurodegenerative disorders that involve the death of specific populations of neurons (see details in respective chapters). Studies of patients and animal and culture models have provided considerable insight in the cellular and molecular mechanisms responsible for synaptic dysfunction and neuronal degeneration in each disorder [18], In Alzheimer s disease, abnormalities in proteolytic processing of the amyloid precursor protein, due to gene... 

Li, T., Ma, G., Cai, H. etal. Nicastrin is required for assembly of presenilin/gamma-secretase complexes to mediate notch signaling and for processing and trafficking of beta-amyloid precursor protein in mammals. /. Neurosci. 23 3272-3277, 2003. 

The Ras proteins are synthesized as biologically inactive, cytosolic precursor proteins. They are then modified by several post-translational processing steps at the carboxyl terminal end and thereby converted into biologically active proteins localized at the plasma membrane. The cysteine of the C-terminal CAAX sequence (C is cysteine, A is generally an aliphatic amino acid, and X is methionine, serine, alanine, or glutamine) is first enzymatically S-farnesylated the AAX part is then cleaved off by a specific protease, and the free C-terminal cysteine is finally converted into a methyl ester (Scheme 1). 

Figure 17.5. The precursor molecule APP and the three different proteases a, (i, y secretase that are involved in the processing of APPto fS-amyloid peptide. The aberrant processing of the amyloid precursor protein (APP) leads to accumulation of beta-amyloid fragments, first as protofibrils and then as fibers that aggregate in the senile plaque structures. (See color insert.)...

Wilquet, V. and De Strooper, B. (2004) Amyloid-beta precursor protein processing in neurodegeneration, Curr. Opin. Neurobiol., 14, 582-588. 

CD, as produced by breast cancer cells in vitro, can exist in multiple molecular-weight forms. It is initially synthesized as an Mt 52,000 protein. This precursor protein is transported to lysosomes, where it is processed to an intermediate 48-kDa protein. The 48-kDa form is later converted into mature forms with molecular weights of 34,000 and 14,000 (R3). Processing of CD appears to be slower in cancer cells than in normal cells (R3). As a result, cancer cells accumulate greater proportions of the 52 kDa and 48 kDa forms than do nonmalignant cells (R3). 

CiECHANOVER, A., et al., Mechanisms of ubiquitin-mediated, limited processing of the NF-kB1 precursor protein pl05. Biochimie, 2001, 83(3—... 

Palombella, V. f., Rando, O. f., Goldberg, A. L., and Maniatis, T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell 1994,... 

The ubiquitin-proteasome pathway is required for processing fh NF-kBl precursor protein and the activation of NF-kB. Cell 1994, 78, 773-785. 

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