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  - Hennrich, Marco L.
A1  - Romanov, Natalie
A1  - Horn, Patrick
A1  - Jaeger, Samira
A1  - Eckstein, Volker
A1  - Steeples, Violetta
A1  - Ye, Fei
A1  - Ding, Ximing
A1  - Poisa-Beiro, Laura
A1  - Mang, Ching Lai
A1  - Lang, Benjamin
A1  - Boultwood, Jacqueline
A1  - Luft, Thomas
A1  - Zaugg, Judith B.
A1  - Pellagatti, Andrea
A1  - Bork, Peer
A1  - Aloy, Patrick
A1  - Gavin, Anne-Claude
A1  - Ho, Anthony D.
T1  - Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
JF  - Nature Communications
N2  - Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models.
KW  - ageing
KW  - haematopoietic stem cells
KW  - mesenchymal stem cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319877
VL  - 9
ER  -