4PCW

Crystal Structure of the N-terminal Domain of Human Profilaggrin at 2.2 A Resolution

Summary for 4PCW

• Entry DOI: 10.2210/pdb4pcw/pdb
• Descriptor: Filaggrin, CALCIUM ION, NONAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: s100 protein, ef-hand calcium binding protein, epidermal skin protein, signaling protein, metal binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasmic granule : P20930
• Total number of polymer chains: 4
• Total formula weight: 45993.19

Authors

Bunick, C.G.,Steitz, T.A. (deposition date: 2014-04-16, release date: 2015-04-01, Last modification date: 2023-09-27)

Primary citation

Bunick, C.G.,Presland, R.B.,Lawrence, O.T.,Pearton, D.J.,Milstone, L.M.,Steitz, T.A.
Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27.
J. Invest. Dermatol., 135:1801-1809, 2015

PubMed 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.

PubMed: 25760235
DOI: 10.1038/jid.2015.102

Experimental method

X-RAY DIFFRACTION (2.2 Å)