FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins

Faraz M. Harsini, Sukanya Chebrolu, Kerry L. Fuson, Mark White, Anne M. Rice, R. Bryan Sutton

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Ferlin proteins participate in such diverse biological events as vesicle fusion in C. elegans, fusion of myoblast membranes to form myotubes, Ca2+-sensing during exocytosis in the hair cells of the inner ear, and Ca2+-dependent membrane repair in skeletal muscle cells. Ferlins are Ca2+-dependent, phospholipid-binding, multi-C2 domain-containing proteins with a single transmembrane helix that spans a vesicle membrane. The overall domain composition of the ferlins resembles the proteins involved in exocytosis; therefore, it is thought that they participate in membrane fusion at some level. But if ferlins do fuse membranes, then they are distinct from other known fusion proteins. Here we show that the central FerA domain from dysferlin, myoferlin, and otoferlin is a novel four-helix bundle fold with its own Ca2+-dependent phospholipid-binding activity. Small-angle X-ray scattering (SAXS), spectroscopic, and thermodynamic analysis of the dysferlin, myoferlin, and otoferlin FerA domains, in addition to clinically-defined dysferlin FerA mutations, suggests that the FerA domain interacts with the membrane and that this interaction is enhanced by the presence of Ca2+.

Original languageEnglish (US)
Article number10949
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Membrane Fusion Proteins
Membrane Fusion
Membranes
Exocytosis
Phospholipids
Proteins
Myoblasts
Skeletal Muscle Fibers
Inner Ear
Thermodynamics
Muscle Cells
Skeletal Muscle
X-Rays
Mutation

ASJC Scopus subject areas

  • General

Cite this

FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins. / Harsini, Faraz M.; Chebrolu, Sukanya; Fuson, Kerry L.; White, Mark; Rice, Anne M.; Sutton, R. Bryan.

In: Scientific Reports, Vol. 8, No. 1, 10949, 01.12.2018.

Research output: Contribution to journalArticle

Harsini, Faraz M. ; Chebrolu, Sukanya ; Fuson, Kerry L. ; White, Mark ; Rice, Anne M. ; Sutton, R. Bryan. / FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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