6gbu
From Proteopedia
Crystal structure of the second SH3 domain of FCHSD2 (SH3-2) in complex with the fourth SH3 domain of ITSN1 (SH3d)
Structural highlights
Function[ITSN1_HUMAN] Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1.[1] [2] Publication Abstract from PubMedMultiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. FCHSD2 deletion leads to decreased ligand uptake caused by slowed pit maturation. FCHSD2 is recruited to endocytic pits by the scaffold protein intersectin via an unusual SH3-SH3 interaction. Here, its flat F-BAR domain binds to the planar region of the plasma membrane surrounding the developing pit forming an annulus. When bound to the membrane, FCHSD2 activates actin polymerization by a mechanism that combines oligomerization and recruitment of N-WASP to PI(4,5)P2, thus promoting pit maturation. Our data therefore describe a molecular mechanism for linking spatiotemporally the plasma membrane to a force-generating actin platform guiding endocytic vesicle maturation. A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.,Almeida-Souza L, Frank RAW, Garcia-Nafria J, Colussi A, Gunawardana N, Johnson CM, Yu M, Howard G, Andrews B, Vallis Y, McMahon HT Cell. 2018 Jun 4. pii: S0092-8674(18)30597-X. doi: 10.1016/j.cell.2018.05.020. PMID:29887380[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Almeida-Souza, L | Andrews, B | Colussi, A | Frank, R | Garcia-Nafria, J | Gunawardana, N | Howard, G | Johnson, C M | McMahon, H T | Vallis, Y | Yu, M | Endocytosis | Sh3-sh3 complex