5jp2
Fcho1 Mu homology domain (Danio Rerio) with bound Eps15 peptideFcho1 Mu homology domain (Danio Rerio) with bound Eps15 peptide
Structural highlights
DiseaseEPS15_HUMAN Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein. FunctionEPS15_HUMAN Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.[1] [2] [3] [4] Publication Abstract from PubMedClathrin-coated vesicles form by rapid assembly of discrete coat constituents into a cargo-sorting lattice. How the sequential phases of coat construction are choreographed is unclear, but transient protein-protein interactions mediated by short interaction motifs are pivotal. We show that arrayed Asp-Pro-Phe (DPF) motifs within the early-arriving endocytic pioneers Eps15/R are differentially decoded by other endocytic pioneers Fcho1/2 and AP-2. The structure of an Eps15/RFcho1 mu-homology domain complex reveals a spacing-dependent DPF triad, bound in a mechanistically distinct way from the mode of single DPF binding to AP-2. Using cells lacking FCHO1/2 and with Eps15 sequestered from the plasma membrane, we establish that without these two endocytic pioneers, AP-2 assemblies are fleeting and endocytosis stalls. Thus, distinct DPF-based codes within the unstructured Eps15/R C terminus direct the assembly of temporary Fcho1/2Eps15/RAP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement. Transient Fcho1/2Eps15/RAP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding.,Ma L, Umasankar PK, Wrobel AG, Lymar A, McCoy AJ, Holkar SS, Jha A, Pradhan-Sundd T, Watkins SC, Owen DJ, Traub LM Dev Cell. 2016 Jun 6;37(5):428-43. doi: 10.1016/j.devcel.2016.05.003. Epub 2016, May 26. PMID:27237791[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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