4PCW

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

4PCW の概要

• エントリーDOI: 10.2210/pdb4pcw/pdb
• 分子名称: Filaggrin, CALCIUM ION, NONAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: s100 protein, ef-hand calcium binding protein, epidermal skin protein, signaling protein, metal binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasmic granule : P20930
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45993.19

構造登録者

Bunick, C.G.,Steitz, T.A. (登録日: 2014-04-16, 公開日: 2015-04-01, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)