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

Scientific Reports
Faraz M HarsiniR Bryan Sutton

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+.

References

Oct 1, 1988·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·V S SauroK P Strickland
Sep 1, 1989·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·R J PrzybylskiA C Kirby
Nov 1, 1994·Protein Science : a Publication of the Protein Society·M MunsonL Regan
Feb 27, 1999·Nature Structural Biology·K M FiebigA T Brunger
May 24, 2001·Biophysical Journal·D I SvergunM H Koch
Apr 18, 2002·The Journal of Biological Chemistry·Dawn Belt DavisElizabeth M McNally
May 9, 2003·Nature·Dimple BansalKevin P Campbell
Nov 11, 2005·Development·Katherine R DohertyElizabeth M McNally
Jun 1, 2006·Journal of Cell Science·Nicole L Washington, Samuel Ward
Mar 28, 2007·BMC Developmental Biology·Michelle K Smith, Barbara T Wakimoto
Apr 5, 2007·Nature Protocols·Norma J Greenfield
Oct 15, 2008·Human Mutation·Martin KrahnNicolas Lévy
Dec 2, 2008·Nature Cell Biology·Chuanxi CaiJianjie Ma
Jul 30, 2010·BMC Evolutionary Biology·Angela LekSandra T Cooper
Oct 6, 2010·The Journal of Cell Biology·Colin P Johnson, Edwin R Chapman
Oct 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maryline BeurgDidier Dulon
Jan 11, 2011·Journal of Molecular Biology·Sarah HelfmannEllen Reisinger
Apr 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ellen ReisingerTobias Moser
Apr 28, 2011·European Journal of Human Genetics : EJHG·Mafalda CacciottoloVincenzo Nigro
May 17, 2011·Physical Biology·Zhe ZhangEmil Alexov
Jun 7, 2011·Nature Structural & Molecular Biology·Enfu HuiEdwin R Chapman
Apr 27, 2013·Nature·Robert P Rambo, John A Tainer
Jun 12, 2013·Communicative & Integrative Biology·Michael E Fealey, Anne Hinderliter
Sep 17, 2013·Structure·Yifan SongDavid Baker
Jan 21, 2014·BMC Structural Biology·Altin SulaNicholas H Keep
Apr 11, 2014·Proceedings of the National Academy of Sciences of the United States of America·Kayleigh A SwaggartElizabeth M McNally
Jul 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Maria AmpraziMichael Kokkinidis
Oct 11, 2014·Nucleic Acids Research·Ivica LetunicPeer Bork
Apr 1, 2012·Journal of Applied Crystallography·Maxim V PetoukhovDmitri I Svergun
Apr 14, 2015·Virology·Stephen C Harrison
Mar 24, 2016·Biochimica Et Biophysica Acta·Sanja Pöyry, Ilpo Vattulainen

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Citations

Feb 29, 2020·Cells·Anna V Bulankina, Sven Thoms
Dec 13, 2019·BioMed Research International·Yimin DongFeng Li
Aug 25, 2019·Cells·Olivier PeulenVincent Castronovo
Dec 2, 2020·Genes·Barbara VonaEllen Reisinger

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Datasets Mentioned

BETA
AAC63519.1
AAF27177.1

Methods Mentioned

BETA
NMR
circular
X-ray
IEC
circular dichroism
protein folding

Software Mentioned

NanoAnalyze
2QUP
Image Lab
Modeller
Robetta
DichroWeb
GeneWiz
SAXLab
DATGNOM
CRYSOL

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