Publications by authors named "Tracy A Caldwell"

4 Publications

  • Page 1 of 1

Low- q Bicelles Are Mixed Micelles.

J Phys Chem Lett 2018 Aug 25;9(15):4469-4473. Epub 2018 Jul 25.

Department of Chemistry , University of Virginia , Charlottesville , Virginia 22904 , United States.

Bicelles are used in many membrane protein studies because they are thought to be more bilayer-like than micelles. We investigated the properties of "isotropic" bicelles by small-angle neutron scattering, small-angle X-ray scattering, fluorescence anisotropy, and molecular dynamics. All data suggest that bicelles with a q value below 1 deviate from the classic bicelle that contains lipids in the core and detergent in the rim. Thus not all isotropic bicelles are bilayer-like.
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http://dx.doi.org/10.1021/acs.jpclett.8b02079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353637PMC
August 2018

A novel FLNC frameshift and an OBSCN variant in a family with distal muscular dystrophy.

PLoS One 2017 26;12(10):e0186642. Epub 2017 Oct 26.

Molecular Medicine Section, Department of Molecular and Developmental Medicine, University of Siena and Azienda Ospedaliera Universitaria Senese, Siena, Italy.

A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by ~15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186642PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657976PMC
November 2017

Characterization of the structure and catalytic activity of Legionella pneumophila VipF.

Proteins 2016 10 5;84(10):1422-30. Epub 2016 Jul 5.

Department of Chemistry and Biochemistry, James Madison University, Harrisonburg, Virginia, 22807.

The pathogenic bacteria Legionella pneumophila is known to cause Legionnaires' Disease, a severe pneumonia that can be fatal to immunocompromised individuals and the elderly. Shohdy et al. identified the L. pneumophila vacuole sorting inhibitory protein VipF as a putative N-acetyltransferase based on sequence homology. We have characterized the basic structural and functional properties of VipF to confirm this original functional assignment. Sequence conservation analysis indicates two putative CoA-binding regions within VipF. Homology modeling and small angle X-ray scattering suggest a monomeric, dual-domain structure joined by a flexible linker. Each domain contains the characteristic beta-splay motif found in many acetyltransferases, suggesting that VipF may contain two active sites. Docking experiments suggest reasonable acetyl-CoA binding locations within each beta-splay motif. Broad substrate screening indicated that VipF is capable of acetylating chloramphenicol and both domains are catalytically active. Given that chloramphenicol is not known to be N-acetylated, this is a surprising finding suggesting that VipF is capable of O-acetyltransferase activity. Proteins 2016; 84:1422-1430. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/prot.25087DOI Listing
October 2016

Mechanical dissociation of the M-band titin/obscurin complex is directionally dependent.

FEBS Lett 2015 Jul 19;589(15):1735-9. Epub 2015 May 19.

Department of Chemistry and Biochemistry, James Madison University, 901 Carrier Dr., Harrisonburg, VA 22807, United States. Electronic address:

Titin and obscurin, two giant muscle proteins, bind to each other in an antiparallel Ig-Ig fashion at the M-band. This interaction must be able to withstand the mechanical strain that the M-band typically experiences and remain intact. The mechanical force on these domains is likely exerted along one of two axes: a longitudinal axis, resulting in a 'shearing' force, or a lateral axis, resulting in a 'peeling' force. Here we present molecular dynamics data suggesting that these forces result in distinct unraveling pathways of the titin/obscurin complex and that peeling the domains apart requires less work and force.
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http://dx.doi.org/10.1016/j.febslet.2015.05.023DOI Listing
July 2015