TY  - JOUR
A1  - Dunce, James M.
A1  - Milburn, Amy E.
A1  - Gurusaran, Manickam
A1  - da Cruz, Irene
A1  - Sen, Lee T.
A1  - Benavente, Ricardo
A1  - Davies, Owen R.
T1  - Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1
JF  - Nature Communications
N2  - Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate.
KW  - DNA
KW  - meiosis
KW  - proteins
KW  - super-resolution microscopy
KW  - X-ray crystallography
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226416
VL  - 9
ER  - 
TY  - JOUR
A1  - Sarukhanyan, Edita
A1  - Shityakov, Sergey
A1  - Dandekar, Thomas
T1  - In silico designed Axl receptor blocking drug candidates against Zika virus infection
JF  - ACS Omega
N2  - After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.
KW  - free energy
KW  - molecular docking
KW  - molecular dynamics
KW  - simulation
KW  - pharmacology
KW  - proteins
KW  - structure-activity relationship
KW  - viruses
KW  - Zika virus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176739
VL  - 3
IS  - 5
ER  -