Binding Sites for Hsp70 Molecular Chaperones in Natural Proteins (original) (raw)

  1. M.-J. Gething1,
  2. S. Blond-Elguindi2,
  3. J. Buchner3,
  4. A. Fourie4,
  5. G. Knarr3,
  6. S. Modrow5,
  7. L. Nanu6,
  8. M. Segal6, and
  9. J. Sambrook7
  10. 1Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia; 2Department of Pharmaceutical Biotechnology, University of Illinois at Chicago, Illinois 60612; 3Institut für Biophysik und Physikalische Biochemie, Universitet Regensburg, 93040 Regensburg, Germany; 4The R.W. Johnson Pharmaceutical Research Institute, San Diego, California 94121; 5Klinische Mikrobiologie, Klinikum der Universitet Regensburg, 93040 Regensburg, Germany, 6University of Texas Southwestern Medical Center, Dallas, Texas 75235; 7Peter MacCallum Cancer Institute, St. Andrew's Place, Melbourne 3002, Australia

Excerpt

Hsp70 molecular chaperones perform numerous functions in cells, including stabilizing newly synthesized or unfolding polypeptides, facilitating translocation of nascent chains across membranes, mediating assembly or disassembly of multimeric protein complexes, and targeting proteins for degradation within lysosomes (for review, see Gething and Sambrook 1992; McKay 1993; Becker and Craig 1994). These functions require that chaperone proteins recognize and bind to a wide variety of target proteins that share no obvious sequence similarity, and that they are able to distinguish native from unfolded proteins.

Although Hsp70 proteins have been highly conserved evolutionarily (Boorstein et al. 1994), they are not functionally interchangeable. For example, neither the endoplasmic reticulum (ER) Hsp70 protein, BiP, nor the bacterial Hsp70 protein, DnaK, can substitute for cytosolic Hsc70 in binding to peptide sequences that target proteins for lysosomal degradation (Terlecky et al. 1992) or in facilitating in vitro translocation of proteins into mammalian microsomes (Wiech et al....