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- Title
Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27.
- Authors
Bunick, Christopher G; Presland, Richard B; Lawrence, Owen T; Pearton, David J; Milstone, Leonard M; Steitz, Thomas A
- Abstract
The fused-type S100 protein profilaggrin and its proteolytic products including filaggrin are important in the formation of a normal epidermal barrier; however, the specific function of the S100 calcium-binding domain in profilaggrin biology is poorly understood. To explore its molecular function, we determined a 2.2 Å-resolution crystal structure of the N-terminal fused-type S100 domain of human profilaggrin with bound calcium ions. The profilaggrin S100 domain formed a stable dimer, which contained two hydrophobic pockets that provide a molecular interface for protein interactions. Biochemical and molecular approaches demonstrated that three proteins, annexin II/p36, stratifin/14-3-3 sigma, and heat shock protein 27, bind to the N-terminal domain of human profilaggrin; one protein (stratifin) co-localized with profilaggrin in the differentiating granular cell layer of human skin. Together, these findings suggest a model where the profilaggrin N-terminus uses calcium-dependent and calcium-independent protein-protein interactions to regulate its involvement in keratinocyte terminal differentiation and incorporation into the cornified cell envelope.
- Subjects
PROFILAGGRIN; CRYSTAL structure; PROTEOLYSIS; CALCIUM ions; KERATINOCYTES; MOLECULAR biology
- Publication
Journal of Investigative Dermatology, 2015, Vol 135, Issue 7, p1801
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2015.102