Heat Shock Protein 47 (HSP47)

Abstract

Heat shock protein 47 (HSP47), a noninhibitory serine protease inhibitor (SERPIN, clade H1) family member, is a unique collagen‐specific molecular chaperone. The binding of HSP47 to collagen has been the subject of intense investigation, as it binds to and only to collagen. This binding specificity presents a relatively unexplored potential of using HSP47 as a target for treatment of collagen‐related diseases and abnormalities. Homology model studies and structural determination have revealed the important amino acid residues for HSP47‐collagen binding interaction. HSP47‐knockout experiment in mice proved the importance of HSP47 for correct folding of collagen triple helices, thus critical for normal development. Various diagnostic and treatment strategies based on the unique HSP47 functions are now being investigated and proposed.

Key Concepts

  • Many heat shock proteins (HSPs) act as molecular chaperones to counter the damaging effects of heat, for example unfolding, aggregation and degradation.
  • HSP47 is a collagen‐specific chaperone, essential for collagen biosynthesis.
  • HSP47 binding and release is pH‐dependent, with the involvement of His residues that governs the release.
  • HSP47 has the potential to be used as diagnostic and therapeutic targets in various diseases and abnormalities.
  • HSP47 modulators and inhibitors are under extensive investigation due to its therapeutic potential in many types of diseases.

Keywords: HSP47; heat shock proteins; collagen; pH‐change

Figure 1. Crystal structure of canine HSP47, showing two molecules of HSP47 bound to one collagen mimetic peptide molecule. All His residues are shown in spheres representation, with the important residues for collagen binding and release highlighted.
Figure 2. Proposed functions of HSP47 during collagen processing.
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Further Reading

An B, Lin Y‐S and Brodsky B (2016) Collagen interactions: drug design and delivery. Advanced Drug Delivery Reviews 97: 69–84.

Kumar A, Bhandari A, Sarde SJ, et al. (2017) Ancestry & molecular evolutionary analyses of heat shock protein 47 kDa (HSP47/SERPINH1). Scientific Reports 7: 10394.

Miller AD (2016) Precision active pharmaceutical ingredients are the goal. Future Medicinal Chemistry 8: 1209–1238.

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Ibrahim, Fatin Hazwani, Abd Latip, Normala, and Abdul‐Wahab, Mohd Firdaus(Apr 2018) Heat Shock Protein 47 (HSP47). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028005]