Open Conformation of Ezrin Bound to Phosphatidylinositol 4,5-Bisphosphate and to F-actin Revealed by Neutron Scattering

Jayasundar, Jayant James; Ju, Jeong Ho; He, Lilin; Liu, Dazhi; Meilleur, Flora; Zhao, Jinkui; Callaway, David J.E.; Bu, Zimei

doi:10.1074/jbc.m112.380972

Cited by 44 publications

(63 citation statements)

References 90 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar result has been obtained via small-angle neutron scattering (SANS) using deuterated ezrin [48]. Thus, the central α-helical domain forms a coiled-coil that extends from the FERM domain which is consistent with SAXS and CD data.…”

Section: Discussionsupporting

confidence: 74%

“…4A inset). We note that a previous study failed to distinguish between the ezrin monomer and dimer via SAXS [48]. The reason for this appears to be the Q ranged used in the previous study, which had a lower limit of 0.014 Å -1 and hence the key difference between monomer and dimer SAXS (the upsweep below 0.02 Å -1 ) is effectively missing in their data.…”

Section: Solution Structure Of Full-length Ezrin Monomer and Dimer Bymentioning

confidence: 64%

See 1 more Smart Citation

Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin

Phang

Harrop

Duff

et al. 2016

Biochemical Journal

View full text Add to dashboard Cite

Ezrin is a member of the ERM (ezrin–radixin–moesin) family of proteins that have been conserved through metazoan evolution. These proteins have dormant and active forms, where the latter links the actin cytoskeleton to membranes. ERM proteins have three domains: an N-terminal FERM [band Four-point-one (4.1) ERM] domain comprising three subdomains (F1, F2, and F3); a helical domain; and a C-terminal actin-binding domain. In the dormant form, FERM and C-terminal domains form a stable complex. We have determined crystal structures of the active FERM domain and the dormant FERM:C-terminal domain complex of human ezrin. We observe a bistable array of phenylalanine residues in the core of subdomain F3 that is mobile in the active form and locked in the dormant form. As subdomain F3 is pivotal in binding membrane proteins and phospholipids, these transitions may facilitate activation and signaling. Full-length ezrin forms stable monomers and dimers. We used small-angle X-ray scattering to determine the solution structures of these species. As expected, the monomer shows a globular domain with a protruding helical coiled coil. The dimer shows an elongated dumbbell structure that is twice as long as the monomer. By aligning ERM sequences spanning metazoan evolution, we show that the central helical region is conserved, preserving the heptad repeat. Using this, we have built a dimer model where each monomer forms half of an elongated antiparallel coiled coil with domain-swapped FERM:C-terminal domain complexes at each end. The model suggests that ERM dimers may bind to actin in a parallel fashion.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Solution Structure Of Full-length Ezrin Monomer and Dimer Bymentioning

confidence: 64%

Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin

Phang

Harrop

Duff

et al. 2016

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…4E. Similarly, it was reported that conformational opening of ezrin upon binding to PIP2 results in more extensive contacts with Factin (Jayasundar et al, 2012). Since PIP2 localization is restricted to the transcriptionally active regions in the nucleolus, we suggest that a particular hydrophobic proteinlipid-RNA environment might exist in that particular region and contribute to the detergent-resistant nuclear PIP2 pools, which were shown to make up to 40% of the total PIP2 mass (Vann et al, 1997).…”

Section: Pip2 Co-localizes With Rrna Nascent Transcripts In Nucleolimentioning

confidence: 93%

Involvement of PIP2 in RNA Polymerase I transcription

Yıldırım

Castaño

Sobol

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryRNA polymerase I (Pol I) transcription is essential for the cell cycle, growth and protein synthesis in eukaryotes. In the present study, we found that phosphatidylinositol 4,5-bisphosphate (PIP2) is a part of the protein complex on the active ribosomal promoter during transcription. PIP2 makes a complex with Pol I and the Pol I transcription factor UBF in the nucleolus. PIP2 depletion reduces Pol I transcription, which can be rescued by the addition of exogenous PIP2. In addition, PIP2 also binds directly to the pre-rRNA processing factor fibrillarin (Fib), and co-localizes with nascent transcripts in the nucleolus. PIP2 binding to UBF and Fib modulates their binding to DNA and RNA, respectively. In conclusion, PIP2 interacts with a subset of Pol I transcription machinery, and promotes Pol I transcription.

show abstract

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 97%

“…Interestingly, the affinity for the full-length protein or for the FERM domain were comparable, indicating that the C-TER and the α-helix did not impair the interaction. Also another recent study from Jayasundar et al [81] shows using small angle neutron scattering (SANS) that PIP2 in solution (micellar in this case) can interact with ezrin and lead to, more than a conformational change, to full activation, ie ezrin can interact with actin.The conformational change of ezrin evidenced with PIP 2 dispersed in solution can be challenged in a cellular context, as PIP 2 is not available in its soluble form or even in its micellar form. Are such conformational changes present when PIP 2 is inserted in membranes?…”

mentioning

confidence: 97%

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

2013

View full text Add to dashboard Cite

Ezrin, radixin and moesin (ERM) proteins are now more and more recognized to play a key role in a large number of important physiological processes such as morphogenesis, cancer metastasis and virus infection. Several recent reviews extensively discuss their biological functions [1][2][3][4]. In this review, we will first remind the main features of this family of proteins, which are now known as linkers and regulators of the plasma membrane/cytoskeleton linkage. We will then briefly review their implication in pathological processes such as cancer and viral infection. In a second part, we will focus on biochemical and biophysical approaches to study ERM interaction with lipid membranes and conformational change in well-defined environments. In vitro studies using biomimetic lipid membranes, especially large unilamellar vesicles (LUVs), giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) and recombinant proteins help to understand the molecular mechanism of conformational activation of ERM proteins. These tools are aimed to decorticate the different steps of the interaction, to simplify the experiments performed in vivo in much more complex biological environments. KeywordsEzrin; radixin and moesin; biomimetic membranes; phosphoinositol (4,5)-bisphosphate (PIP 2 ); large unilamellar vesicles; supported lipid bilayers; giant unilamelar vesicles Corresponding author: Catherine Picart, CNRS UMR 5628 (LMGP), Grenoble Institute of Technology and CNRS, 3 parvis Louis Néel, F-38016 Grenoble Cedex, France. Europe PMC Funders GroupAuthor Manuscript Biochimie. Author manuscript; available in PMC 2014 July 28. Published in final edited form as:Biochimie. 2013 January ; 95(1): 3-11. doi:10.1016/j.biochi.2012.09.033. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts Biological importance of Ezrin, Radixin and Moesin General overview of ERM proteins (Ezrin, Radixin, Moesin)ERM proteins are localized at the plasma membrane in actin-rich surface structures (Fig 1) [5], such as microvilli, membrane ruffles, and lamellipodia in gut cells, lymphocytes, hepatocytes, spermatozoids, fibroblasts and in a variety of other cell types [5][6][7][8][9]. They are involved in various physiological processes including establishment of cell polarity, cell motility and cell signaling [10]. They act as linkers between the plasma membrane and the cortical actin cytoskeleton. From a structural point of view, ERMs are constituted of 3 domains : a membrane binding domain, also known as FERM (for band 4.1 protein, ezrin, radixin and moesin), and intermediary region and a actin binding domain called C-ERMAD (for C-terminal ERM-association domain) (Fig 2A).The FERM domain, constituted of ~300 amino acids, is characteristic of the proteins of the band 4.1 superfamily. These proteins also present other types of domains, including PDZ, tyrosine phosphatase, SH2-like, tyrosine kinase, kinase-like, myosin head, and PH domains [11]. In ERM proteins, the FERM domain is followed by a long α-helical region, whi...

show abstract

Open Conformation of Ezrin Bound to Phosphatidylinositol 4,5-Bisphosphate and to F-actin Revealed by Neutron Scattering

Cited by 44 publications

References 90 publications

Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin

Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin

Involvement of PIP2 in RNA Polymerase I transcription

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

Contact Info

Product

Resources

About