Epsin and Sla2 form assemblies through phospholipid interfaces
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Epsin and Sla2 form assemblies through phospholipid interfaces. / Garcia-Alai, Maria M; Heidemann, Johannes; Skruzny, Michal; Gieras, Anna; Mertens, Haydyn D T; Svergun, Dmitri I; Kaksonen, Marko; Uetrecht, Charlotte; Meijers, Rob.
In: NAT COMMUN, Vol. 9, No. 1, 23.01.2018, p. 328.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Epsin and Sla2 form assemblies through phospholipid interfaces
AU - Garcia-Alai, Maria M
AU - Heidemann, Johannes
AU - Skruzny, Michal
AU - Gieras, Anna
AU - Mertens, Haydyn D T
AU - Svergun, Dmitri I
AU - Kaksonen, Marko
AU - Uetrecht, Charlotte
AU - Meijers, Rob
PY - 2018/1/23
Y1 - 2018/1/23
N2 - In clathrin-mediated endocytosis, adapter proteins assemble together with clathrin through interactions with specific lipids on the plasma membrane. However, the precise mechanism of adapter protein assembly at the cell membrane is still unknown. Here, we show that the membrane-proximal domains ENTH of epsin and ANTH of Sla2 form complexes through phosphatidylinositol 4,5-bisphosphate (PIP2) lipid interfaces. Native mass spectrometry reveals how ENTH and ANTH domains form assemblies by sharing PIP2 molecules. Furthermore, crystal structures of epsin Ent2 ENTH domain from S. cerevisiae in complex with PIP2 and Sla2 ANTH domain from C. thermophilum illustrate how allosteric phospholipid binding occurs. A comparison with human ENTH and ANTH domains reveal only the human ENTH domain can form a stable hexameric core in presence of PIP2, which could explain functional differences between fungal and human epsins. We propose a general phospholipid-driven multifaceted assembly mechanism tolerating different adapter protein compositions to induce endocytosis.
AB - In clathrin-mediated endocytosis, adapter proteins assemble together with clathrin through interactions with specific lipids on the plasma membrane. However, the precise mechanism of adapter protein assembly at the cell membrane is still unknown. Here, we show that the membrane-proximal domains ENTH of epsin and ANTH of Sla2 form complexes through phosphatidylinositol 4,5-bisphosphate (PIP2) lipid interfaces. Native mass spectrometry reveals how ENTH and ANTH domains form assemblies by sharing PIP2 molecules. Furthermore, crystal structures of epsin Ent2 ENTH domain from S. cerevisiae in complex with PIP2 and Sla2 ANTH domain from C. thermophilum illustrate how allosteric phospholipid binding occurs. A comparison with human ENTH and ANTH domains reveal only the human ENTH domain can form a stable hexameric core in presence of PIP2, which could explain functional differences between fungal and human epsins. We propose a general phospholipid-driven multifaceted assembly mechanism tolerating different adapter protein compositions to induce endocytosis.
KW - Adaptor Proteins, Vesicular Transport
KW - Amino Acid Sequence
KW - Binding Sites
KW - Cell Membrane
KW - Chaetomium
KW - Crystallography, X-Ray
KW - Endocytosis
KW - Fungal Proteins
KW - Humans
KW - Models, Molecular
KW - Phosphatidylinositol 4,5-Diphosphate
KW - Protein Binding
KW - Protein Domains
KW - Protein Multimerization
KW - Saccharomyces cerevisiae
KW - Sequence Homology, Amino Acid
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/s41467-017-02443-x
DO - 10.1038/s41467-017-02443-x
M3 - SCORING: Journal article
C2 - 29362354
VL - 9
SP - 328
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -