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TitleA Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.
Journal, issue, pagesCell, Vol. 174, Issue 2, Page 325-337.e14, Year 2018
Publish dateJul 12, 2018
AuthorsLeonardo Almeida-Souza / Rene A W Frank / Javier García-Nafría / Adeline Colussi / Nushan Gunawardana / Christopher M Johnson / Minmin Yu / Gillian Howard / Byron Andrews / Yvonne Vallis / Harvey T McMahon /
PubMed AbstractMultiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and ...Multiple 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)P, 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.
External linksCell / PubMed:29887380 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.44 - 9.2 Å
Structure data

EMDB-4371:
Cryo-EM map of the FCHSD2 F-BAR domain + SH3-1
Method: EM (single particle) / Resolution: 9.2 Å

PDB-6gbu:
Crystal structure of the second SH3 domain of FCHSD2 (SH3-2) in complex with the fourth SH3 domain of ITSN1 (SH3d)
Method: X-RAY DIFFRACTION / Resolution: 3.44 Å

Source
  • homo sapiens (human)
KeywordsENDOCYTOSIS / SH3-SH3 complex

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