Organization of Farnesylated, Carboxymethylated KRAS4B on Membranes

Eric Barklis, Andrew G. Stephen, August O. Staubus, Robin Lid Barklis, Ayna Alfadhli

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of molecular biology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Membranes
Proteins
Prenylation
ras Proteins
Post Translational Protein Processing
Protein Isoforms
Lipids
Mutation
Neoplasms

Keywords

  • membrane
  • monolayer
  • nanocluster
  • oligomerization
  • RAS

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Organization of Farnesylated, Carboxymethylated KRAS4B on Membranes. / Barklis, Eric; Stephen, Andrew G.; Staubus, August O.; Barklis, Robin Lid; Alfadhli, Ayna.

In: Journal of molecular biology, 01.01.2019.

Research output: Contribution to journalArticle

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