TY  - JOUR
A1  - Sajko, Sara
A1  - Grishkovskaya, Irina
A1  - Kostan, Julius
A1  - Graewert, Melissa
A1  - Setiawan, Kim
A1  - Trübestein, Linda
A1  - Niedermüller, Korbinian
A1  - Gehin, Charlotte
A1  - Sponga, Antonio
A1  - Puchinger, Martin
A1  - Gavin, Anne-Claude
A1  - Leonard, Thomas A.
A1  - Svergun, Dimitri I.
A1  - Smith, Terry K.
A1  - Morriswood, Brooke
A1  - Djinovic-Carugo, Kristina
T1  - Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats
JF  - PLoS One
N2  - MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats-Trypanosoma brucei MORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein from Trypanosoma brucei and homologous proteins from the parasites Toxoplasma gondii and Plasmodium falciparum were obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This enabled a first structure-based definition of the MORN repeat itself. Furthermore, all three structures dimerised via their C-termini in an antiparallel configuration. The dimers could form extended or V-shaped quaternary structures depending on the presence of specific interface residues. This work provides a new perspective on MORN repeats, showing that they are protein-protein interaction modules capable of mediating both dimerisation and oligomerisation.
KW  - recognition nexus domain
KW  - trypanosoma brucei
KW  - blood stream
KW  - phosphatidylserine transport
KW  - biological macromolecules
KW  - membrane occupation
KW  - solution scattering
KW  - molecular cloning
KW  - flagellar pocket
KW  - endocytosis
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231261
VL  - 15
IS  - 23
ER  - 
TY  - JOUR
A1  - Oli, Swarna
A1  - Abdelmohsen, Usama Ramadan
A1  - Hentschel, Ute
A1  - Schirmeister, Tanja
T1  - Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation
JF  - MARINE DRUGS
N2  - In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 mu M and without cytotoxic effects against J774.1 macrophages at 100 mu M concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.
KW  - plakortis halichondroides
KW  - plakortide E.
KW  - protease inhibitor
KW  - slowly-binding reversible inhibitor
KW  - cathepsin
KW  - trypanosoma brucei
KW  - cysteine protease
KW  - malaria parasites
KW  - cathepsin-L
KW  - in-vitro
KW  - rhodesain
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116536
SN  - 1660-3397
VL  - 12
IS  - 5
ER  -