dc.contributor.author | Kalinowski, Agnieszka | |
dc.contributor.author | Yaron, Peter N. | |
dc.contributor.author | Qin, Zhao | |
dc.contributor.author | Shenoy, Siddharth | |
dc.contributor.author | Dahl, Kris Noel | |
dc.contributor.author | Buehler, Markus J | |
dc.contributor.author | Loesche, Mathias | |
dc.date.accessioned | 2017-05-04T20:16:49Z | |
dc.date.available | 2017-05-04T20:16:49Z | |
dc.date.issued | 2014-08 | |
dc.date.submitted | 2014-07 | |
dc.identifier.issn | 03014622 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108675 | |
dc.description.abstract | Hutchinson–Gilford progeria syndrome is a premature aging disorder associated with the expression of ∆50 lamin A (∆50LA), a mutant form of the nuclear structural protein lamin A (LA). ∆50LA is missing 50 amino acids from the tail domain and retains a C-terminal farnesyl group that is cleaved from the wild-type LA. Many of the cellular pathologies of HGPS are thought to be a consequence of protein–membrane association mediated by the retained farnesyl group. To better characterize the protein–membrane interface, we quantified binding of purified recombinant ∆50LA tail domain (∆50LA-TD) to tethered bilayer membranes composed of phosphatidylserine and phosphocholine using surface plasmon resonance. Farnesylated ∆50LA-TD binds to the membrane interface only in the presence of Ca[superscript 2 +] or Mg[superscript 2 +] at physiological ionic strength. At extremely low ionic strength, both the farnesylated and non-farnesylated forms of ∆50LA-TD bind to the membrane surface in amounts that exceed those expected for a densely packed protein monolayer. Interestingly, the wild-type LA-TD with no farnesylation also associates with membranes at low ionic strength but forms only a single layer. We suggest that electrostatic interactions are mediated by charge clusters with a net positive charge that we calculate on the surface of the LA-TDs. These studies suggest that the accumulation of ∆50LA at the inner nuclear membrane observed in cells is due to a combination of aggregation and membrane association rather than simple membrane binding; electrostatics plays an important role in mediating this association. | en_US |
dc.description.sponsorship | National Institute of General Medical Sciences (U.S.) (1R01-GM101647) | en_US |
dc.description.sponsorship | United States. Office of Naval Research. Presidential Early Career Award for Scientists and Engineers (N000141010562) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (U01 EB014976) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.bpc.2014.08.005 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Interfacial binding and aggregation of lamin A tail domains associated with Hutchinson–Gilford progeria syndrome | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Kalinowski, Agnieszka et al. “Interfacial Binding and Aggregation of Lamin A Tail Domains Associated with Hutchinson–Gilford Progeria Syndrome.” Biophysical Chemistry 195 (2014): 43–48. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering | en_US |
dc.contributor.mitauthor | Buehler, Markus J | |
dc.contributor.mitauthor | Loesche, Mathias | |
dc.relation.journal | Biophysical Chemistry | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Kalinowski, Agnieszka; Yaron, Peter N.; Qin, Zhao; Shenoy, Siddharth; Buehler, Markus J.; Lösche, Mathias; Dahl, Kris Noel | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-4173-9659 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |