| 1. |
- Lovelace, Jeffrey J., et al.
(author)
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Protein crystals can be incommensurately modulated
- 2008
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In: Journal of applied crystallography. - 0021-8898 .- 1600-5767. ; 41, s. 600-605
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Journal article (peer-reviewed)abstract
- For a normal periodic crystal, the X-ray diffraction pattern can be described by an orientation matrix and a set of three integers that indicate the reciprocal lattice points. Those integers determine the spacing along the reciprocal lattice directions. In aperiodic crystals, the diffraction pattern is modulated and the standard periodic main reflections are surrounded by satellite reflections. The successful indexing and refinement of the main unit cell and q vector using TWINSOLVE, developed by Svensson [(2003). Lund University, Sweden], are reported here for an incommensurately modulated, aperiodic crystal of a profilin: actin complex. The indexing showed that the modulation is along the b direction in the crystal, which corresponds to an 'actin ribbon' formed by the crystal lattice. Interestingly, the transition to the aperiodic state was shown to be reversible and the diffraction pattern returned to the periodic state during data collection. It is likely that the protein underwent a conformational change that affected the neighbouring profilin: actin molecules in such a way as to produce the observed modulation in the diffraction pattern. Future work will aim to trap the incommensurately modulated crystal state, for example using cryocooling or chemical crosslinking, thus allowing complete X-ray data to be collected.
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| 2. |
- Grenklo, Staffan, et al.
(author)
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Tropomyosin assembly intermediates in the control of MF-system turnover
- 2008
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In: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 87:11, s. 905-920
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Journal article (peer-reviewed)abstract
- Tropomyosin is a coiled-coil α-helical protein, which self-associates in a head-to-tail fashion along polymers of actin to produce thin filaments. Mammalian non-muscle cells express a large number of tropomyosin isoforms, which are differentially regulated during embryogenesis and associated with specialized actin microfilament ensembles in cells. The function of tropomyosin in specifying form and localization of these subcellular structures, and the precise mechanism(s) by which they carry out their functions, is unclear. This paper reports that, while the major fraction of non-muscle cell tropomyosin resides in actin thin filaments of the cytomatrix, the soluble part of the cytoplasm contains tropomyosins in the form of actin-free multimers, which are isoform specific and of high molecular weight (MWapp 180,000–250,000). Stimulation of motile cells with growth factors induces a rapid, actin polymerization-dependent outgrowth of lamellipodia and filopodia. Concomitantly, the levels of tropomyosin isoform-specific multimers decrease, suggesting their involvement in actin thin filament formation. Malignant tumor cells have drastically altered levels and composition of tropomyosin isoform-specific multimers as well as tropomyosin in the cytomatrix.
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| 3. |
- Hillberg, Louise, et al.
(author)
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Tropomyosins are present in lamellipodia of motile cells
- 2006
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In: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 85:5, s. 399-409
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Journal article (peer-reviewed)abstract
- This paper shows that high-molecular-weight tropomyosins (TMs), as well as shorter isoforms of this protein, are present in significant amounts in lamellipodia and filopodia of spreading normal and transformed cells. The presence of TM in these locales was ascertained by staining of cells with antibodies reacting with endogenous TMs and through the expression of hemaglutinin- and green fluorescent protein-tagged TM isoforms. The observations are contrary to recent reports suggesting the absence of TMs in regions,where polymerization of actin takes place, and indicate that the view of the role of TM in the formation of actin filaments needs to be significantly revised.
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| 4. |
- Lindberg, Uno, et al.
(author)
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The microfilament system and malignancy
- 2008
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In: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X .- 1096-3650. ; 18:1, s. 2-11
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Research review (peer-reviewed)abstract
- Increased motile activity, increased rate of cell proliferation and removal of growth inhibiting cell-cell contacts are hallmarks of tumorigenesis. Activation of cell motility and migration is caused by activation of receptors, turning on the growth cycle. Increased expression of metalloproteinases, breaking cell:cell contacts and organ confines, allows the spread of malignant cancer cells to other sites in the organism. It has become increasingly clear that most transmembrane proteins (growth factor receptors, adhesion proteins and ion channels) are either permanently or transiently associated with the sub-membraneous system of actin microfilaments (MF), whose force generating capacity they control. Although there has been great progress in our understanding of the physiological importance of the MF-system, as will be exemplified in this issue of SCB, many aspects of actin microfilament formation and its regulation are still unclear. Redox control of the actin (MF)-system in cell motility and migration and its perturbations in pathophysiology, including cancer, is an emerging field of research.
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| 5. |
- Schutt, Clarence E., et al.
(author)
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A structural model of the profilin–formin pacemaker system for actin filament elongation
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Journal article (peer-reviewed)abstract
- The formins constitute a large class of multi-domain polymerases that catalyze the localization and growth of unbranched actin filaments in cells from yeast to mammals. The conserved FH2 domains form dimers that bind actin at the barbed end of growing filaments and remain attached as new subunits are added. Profilin–actin is recruited and delivered to the barbed end by formin FH1 domains via the binding of profilin to interspersed tracts of poly-L-proline. We present a structural model showing that profilin–actin can bind the FH2 dimer at the barbed end stabilizing a state where profilin prevents its associated actin subunit from directly joining the barbed end. It is only with the dissociation of profilin from the polymerase that an actin subunit rotates and docks into its helical position, consistent with observations that under physiological conditions optimal elongation rates depend on the dissociation rate of profilin, independently of cellular concentrations of actin subunits.
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