RT Journal Article
SR Electronic
T1 Systematic simulation of the interactions of Pleckstrin homology domains with membranes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.16.472954
DO 10.1101/2021.12.16.472954
A1 Le Huray, Kyle I.P.
A1 Wang, He
A1 Sobott, Frank
A1 Kalli, Antreas C.
YR 2021
UL http://biorxiv.org/content/early/2021/12/16/2021.12.16.472954.abstract
AB Pleckstrin homology (PH) domains can recruit proteins to membranes by recognition of phosphatidylinositol phosphates (PIPs). Here we report the systematic simulation of the interactions of 100 mammalian PH domains with PIP containing model membranes. Comparison with crystal structures of PH domains bound to PIP analogues demonstrates that our method correctly identifies interactions at known canonical and non-canonical sites, while revealing additional functionally important sites for interaction not observed in the crystal structure, such as for P-Rex1 and Akt1. At the family level, we find that the β1 and β2 strands and their connecting loop constitute the primary PIP interaction site for the majority of PH domains, but we highlight interesting exceptional cases. Simultaneous interaction with multiple PIPs and clustering of PIPs induced by PH domain binding are also observed. Our findings support a general paradigm for PH domain membrane association involving multivalent interactions with anionic lipids.Teaser Simulating the binding of 100 Pleckstrin homology domains to cell membranes reveals patterns in their lipid interactions.Competing Interest StatementThe authors have declared no competing interest.