| Bibliographic Citation | |
| Full Text |  2 Mb |
|---|---|
| Title | PROTEIN QUALITY CONTROL IN BACTERIAL CELLS: INTEGRATED NETWORKS OF CHAPERONES AND ATP-DEPENDENT PROTEASES. |
| Creator/Author | FLANAGAN,J.M. ; BEWLEY,M.C. |
| Publication Date | 2001 Dec 03 |
| OSTI Identifier | OSTI ID: 789884 |
| Report Number(s) | BNL--68837 |
| DOE Contract Number | AC02-98CH10886 |
| Other Number(s) | TRN: US200202%%382 |
| Resource Type | Book |
| Resource Relation | Other Information: PBD: 3 Dec 2001 |
| Research Org | Brookhaven National Lab., Upton, NY (US) |
| Sponsoring Org | USDOE Office of Energy Research (ER) (US) |
| Subject | 59 BASIC BIOLOGICAL SCIENCES; AMINO ACID SEQUENCE; AMINO ACIDS; BACTERIA; DISEASES; MAINTENANCE; MITOCHONDRIA; POLYPEPTIDES; PROTEINS; QUALITY CONTROL; RESIDUES; RIBOSOMES; SYNTHESIS |
| Description/Abstract | It is generally accepted that the information necessary to specify the native, functional, three-dimensional structure of a protein is encoded entirely within its amino acid sequence; however, efficient reversible folding and unfolding is observed only with a subset of small single-domain proteins. Refolding experiments often lead to the formation of kinetically-trapped, misfolded species that aggregate, even in dilute solution. In the cellular environment, the barriers to efficient protein folding and maintenance of native structure are even larger due to the nature of this process. First, nascent polypeptides must fold in an extremely crowded environment where the concentration of macromolecules approaches 300-400 mg/mL and on average, each ribosome is within its own diameter of another ribosome (1-3). These conditions of severe molecular crowding, coupled with high concentrations of nascent polypeptide chains, favor nonspecific aggregation over productive folding (3). Second, folding of newly-translated polypeptides occurs in the context of their vehtorial synthesis process. Amino acids are added to a growing nascent chain at the rate of -5 residues per set, which means that for a 300 residue protein its N-terminus will be exposed to the cytosol {approx}1 min before its C-terminus and be free to begin the folding process. However, because protein folding is highly cooperative, the nascent polypeptide cannot reach its native state until a complete folding domain (50-250 residues) has emerged from the ribosome. Thus, for a single-domain protein, the final steps in folding are only completed post-translationally since {approx}40 residues of a nascent chain are sequestered within the exit channel of the ribosome and are not available for folding (4). A direct consequence of this limitation in cellular folding is that during translation incomplete domains will exist in partially-folded states that tend to expose hydrophobic residues that are prone to aggregation and/or misfolding. Thus it is not surprising that, in cells, the protein folding process is error prone and organisms have evolved ''editing'' or quality control (QC) systems to assist in the folding, maintenance and, when necessary, selective removal of damaged proteins. In fact, there is growing evidence that failure of these QC-systems contributes to a number of disease states (5-8). This chapter describes our current understanding of the nature and mechanisms of the protein quality control systems in the cytosol of bacteria. Parallel systems are exploited in the cytosol and mitochondria of eukaryotes to prevent the accumulation of misfolded proteins. |
| Publisher | Brookhaven National Laboratory, Upton, NY (US) |
| Country of Publication | United States |
| Language | English |
| Format | Medium: ED; Size: 56 pages |
| Availability | Refer requests to OSTI, Office of Scientific and Technical Information, 175 Oak Ridge Turnpike, Oak Ridge, TN 37830 (US); OSTI as DE00789884 To purchase this media from NTIS, click here |
| System Entry Date | 2008 Feb 05 |
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Last Updated: 05/12/2009