7B2L

Structure of the endocytic adaptor complex AENTH

Summary for 7B2L

• Entry DOI: 10.2210/pdb7b2l/pdb
• EMDB information: 11715 11987
• Descriptor: ENTH domain of epsin Ent1, ANTH domain of Sla2, [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate (3 entities in total)
• Functional Keywords: membrane protein, clathrin-mediated endocytosis, adapter protein, sla2, epsin-1, enth, anth, cell adhesion
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 16
• Total formula weight: 432031.43

Authors

Klebl, D.P.,Lizarrondo, J.,Sobott, F.,Garcia-Alai, M.,Muench, S.P. (deposition date: 2020-11-27, release date: 2021-05-05, Last modification date: 2024-05-01)

Primary citation

Lizarrondo, J.,Klebl, D.P.,Niebling, S.,Abella, M.,Schroer, M.A.,Mertens, H.D.T.,Veith, K.,Thuenauer, R.,Svergun, D.I.,Skruzny, M.,Sobott, F.,Muench, S.P.,Garcia-Alai, M.M.
Structure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis.
Nat Commun, 12:2889-2889, 2021

PubMed Abstract: During clathrin-mediated endocytosis, a complex and dynamic network of protein-membrane interactions cooperate to achieve membrane invagination. Throughout this process in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for successful membrane invagination. Here, we present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP that constitutes the anchor to the plasma membrane. Detailed in vitro and in vivo mutagenesis of the complex interfaces delineate the key interactions for complex formation and deficient cell growth phenotypes demonstrate its biological relevance. A hetero-tetrameric unit binds PIP molecules at the ANTH-ENTH interfaces and can form larger assemblies to contribute to membrane remodeling. Finally, a time-resolved small-angle X-ray scattering study of the interaction of these adaptor domains in vitro suggests that ANTH and ENTH domains have evolved to achieve a fast subsecond timescale assembly in the presence of PIP and do not require further proteins to form a stable complex. Together, these findings provide a molecular understanding of an essential piece in the molecular puzzle of clathrin-coated endocytic sites.

PubMed: 34001871
DOI: 10.1038/s41467-021-23151-7

Experimental method

ELECTRON MICROSCOPY (3.9 Å)