Thursday, October 29, 2009

Heat-shock Proteins Families

Heat-shock proteins are named according to their molecular weight (kilodaltons):

Approximate molecular weight (kDa) Eukaryotic proteins Function
10 kDa Hsp10 Co-factor of Hsp60. Chaperonins: protein complexes that assist the folding of these nascent, non-native polypeptides into their native, functional state.
20-30 kDa The HspB group of Hsp. Ten members in mammals including Hsp27 or HspB1
40 kDa Hsp40 Co-factor of Hsp70
60 kDa Hsp60 Involved in protein folding after its post-translational import to the mitochondrion/chloroplast
70 kDa The HspA group of Hsp including Hsp71, Hsp70, Hsp72, Grp78 (BiP), Hsx70 found only in primates Protein folding and unfolding, provides thermotolerance to cell on exposure to heat stress. Also prevents protein folding during post-translational import into the mitochondria/chloroplast.
90 kDa The HspC group of Hsp including Hsp90, Grp94 Maintenance of steroid receptors and transcription factors
100 kDa Hsp104, Hsp110 Tolerance of extreme temperature

The Hsp70/Hsp40 Family (Chaperone)

The 70 kilodalton heat shock proteins (Hsp70s) are a family of highly-related protein isoforms ranging in size from 66 kDa to 78 kDa. Proteins with similar structure exist in virtually all living organisms. The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress. The various family members are distributed throughout different intracellular compartments but nevertheless share many structural and biochemical properties.

These include: the cytosolic/nuclear Hsp70 proteins Hsc70 (a.k.a. Hsp73) and Hsp70 (a.k.a. Hsp72), Grp78 or Bip present within the lumen of the endoplasmic reticulum, and Grp75 (also called mortalin) localized within mitochondria. Hsc70 is constitutively expressed and poorly stress-inducible, whereas Hsp70 is unabundant in normal physiological situations and strongly induced under oxidative stress. Hsc70 was placed in the heat shock protein family due to homology with other heat shock proteins.

All of the mammalian Hsp70 family members require one or more cochaperones for their reaction cycle (HSP40 or HSP100).

The Hsp60/Hsp10 Family (Chaperonins)

The HSP60 (GroEL - Prokaryotic) proteins in combination with its particular co-factor Hsp10 (GroES - Prokaryotic) bind newly synthesized polypeptides and facilitate their folding to the native state in an ATP-dependent cycle. The binding and sequestration of the substrate polypeptide occurs within the large central cavity of the chaperonin complex. It is thought that protection of the substrate protein within the central cavity of the chaperonin provides a sequestered protein folding environment, thereby reducing the probability of misfolding and aggregation of the target protein with other polypeptides. The chaperonins together with Hsp70 chaperones coordinate the efficient folding and assembly of many proteins throughout the cell.

Hsp60 families are highly immunogenic proteins. The related GroEL proteins from different pathogens elicit strong humoral and cellular immune responses.

In mammalian the Hsp60 is localized within mitochondria and with its cochaperone, Hsp10, participates in the folding and assembly of newly synthesized proteins as they are transported into the mitochondria from the cytosol.

Hsp90

Hsp90 is a molecular chaperone and is one of the most abundant proteins expressed in cells. Unlike some of the other well characterized heat shock proteins whose chaperone role involves their interaction with many cellular proteins, Hsp90 exhibits some selectivity for a distinct set of “client” proteins. Hsp90 interacts with a variety of protein kinases and transcription factors important for growth and development. Working with its very large number of cochaperones, Hsp90 appears to maintain its client proteins in a conformation that allows for their subsequent activation in response to appropriate growth signals. Not surprisingly, Hsp90 and its co-chaperones are at the forefront of research for those studying signal transduction events and cancer.

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