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Publication Abstract from PubMed

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 A-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 Hsp27, 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.Journal of Investigative Dermatology accepted article preview online, 11 March 2015. doi:10.1038/jid.2015.102.

Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin and hsp27.,Bunick CG, Presland RB, Lawrence OT, Pearton DJ, Milstone LM, Steitz TA J Invest Dermatol. 2015 Mar 11. doi: 10.1038/jid.2015.102. PMID:25760235^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.