ER/K-link—Leveraging a native protein linker to probe dynamic cellular interactions

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations


ER/K α-helices are a subset of single alpha helical domains, which exhibit unusual stability as isolated protein secondary structures. They adopt an elongated structural conformation, while regulating the frequency of interactions between proteins or polypeptides fused to their ends. Here we review recent advances on the structure, stability and function of ER/K α-helices as linkers (ER/K linkers) in native proteins. We describe methodological considerations in the molecular cloning, protein expression and measurement of interaction strengths, using sensors incorporating ER/K linkers. We highlight biological insights obtained over the last decade by leveraging distinct biophysical features of ER/K-linked sensors. We conclude with the outlook for the use of ER/K linkers in the selective modulation of dynamic cellular interactions.

Original languageEnglish (US)
Title of host publicationLinkers in Biomacromolecules
EditorsMaarten Merkx
PublisherAcademic Press Inc.
Number of pages36
ISBN (Print)9780128208182
StatePublished - Jan 2021

Publication series

NameMethods in Enzymology
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Bibliographical note

Funding Information:
We acknowledge funding from the NIH (R35-GM126940 and R01-GM117923 to S.S.)

Publisher Copyright:
© 2021 Elsevier Inc.


  • ER/K linker
  • FRET biosensors
  • GPCR
  • Kinases
  • Protein-protein interactions
  • Signaling
  • Single alpha helix
  • Protein Conformation, alpha-Helical
  • Peptides/genetics
  • Protein Structure, Secondary
  • Models, Molecular
  • Proteins/genetics

PubMed: MeSH publication types

  • Review
  • Journal Article
  • Research Support, N.I.H., Extramural


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