4pcw

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

spinqualitylabelsall models 4pcw, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pcw is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2PE, CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FILA_HUMAN Autosomal dominant ichthyosis vulgaris. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Function FILA_HUMAN Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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