@article{75bf3d73d30d4ba18278168cd3166d6f,
title = "Organization of Farnesylated, Carboxymethylated KRAS4B on Membranes",
abstract = "Mutations of the Ras proteins HRAS, KRAS4A, KRAS4B, and NRAS are associated with a high percentage of all human cancers. The proteins are composed of highly homologous N-terminal catalytic or globular domains, plus C-terminal hypervariable regions (HVRs). Post-translational modifications of all RAS HVRs helps target RAS proteins to cellular membrane locations where they perform their signaling functions. For the predominant KRAS4 isoform, KRAS4B, post-translational farnesylation and carboxymethylation, along with a patch of HVR basic residues help foster membrane binding. Recent investigations implicate membrane-bound RAS dimers, oligomers, and nanoclusters as landing pads for effector proteins that relay RAS signals. The details of these RAS signaling platforms have not been elucidated completely, in part due to the difficulties in preparing modified proteins. We have employed properly farnesylated and carboxymethylated KRAS4B in lipid monolayer incubations to examine how the proteins assemble on membranes. Our results reveal novel insights into to how KRAS4B may organize on membranes.",
keywords = "RAS, membrane, monolayer, nanocluster, oligomerization",
author = "Eric Barklis and Stephen, {Andrew G.} and Staubus, {August O.} and Barklis, {Robin Lid} and Ayna Alfadhli",
note = "Funding Information: These investigations were supported by the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533 and by the OHSU Center for Spatial Systems Biomedicine . E.B., A.O.S., R.L.B., and A.A. also received support from the National Institutes of Health under grant R01 GM060170 . This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health Contract HHSN261200800001E. We thank Vanessa Wall, Angela Carter, Kelly Snead, and Peter Frank from the NCI-RAS Initiative for production of farnesylated and methylated KRas4b protein used in this work. We are grateful for helpful advice and assistance from James Chen, David Farrens, Claudia Lopez, Xiaolin Nan, Jonathan Pruneda, Ujwal Shinde, Philip Stork, and Robin Woolman. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Funding Information: These investigations were supported by the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533 and by the OHSU Center for Spatial Systems Biomedicine. E.B. A.O.S. R.L.B. and A.A. also received support from the National Institutes of Health under grant R01 GM060170. This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health Contract HHSN261200800001E. We thank Vanessa Wall, Angela Carter, Kelly Snead, and Peter Frank from the NCI-RAS Initiative for production of farnesylated and methylated KRas4b protein used in this work. We are grateful for helpful advice and assistance from James Chen, David Farrens, Claudia Lopez, Xiaolin Nan, Jonathan Pruneda, Ujwal Shinde, Philip Stork, and Robin Woolman. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Declaration of Competing Interest: None. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = sep,
day = "6",
doi = "10.1016/j.jmb.2019.07.025",
language = "English (US)",
volume = "431",
pages = "3706--3717",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "19",
}