@article{SajkoGrishkovskayaKostanetal.2020, author = {Sajko, Sara and Grishkovskaya, Irina and Kostan, Julius and Graewert, Melissa and Setiawan, Kim and Tr{\"u}bestein, Linda and Niederm{\"u}ller, Korbinian and Gehin, Charlotte and Sponga, Antonio and Puchinger, Martin and Gavin, Anne-Claude and Leonard, Thomas A. and Svergun, Dimitri I. and Smith, Terry K. and Morriswood, Brooke and Djinovic-Carugo, Kristina}, title = {Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {23}, doi = {10.1371/journal.pone.0242677}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231261}, year = {2020}, abstract = {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.}, language = {en} } @article{HennrichRomanovHornetal.2018, author = {Hennrich, Marco L. and Romanov, Natalie and Horn, Patrick and Jaeger, Samira and Eckstein, Volker and Steeples, Violetta and Ye, Fei and Ding, Ximing and Poisa-Beiro, Laura and Mang, Ching Lai and Lang, Benjamin and Boultwood, Jacqueline and Luft, Thomas and Zaugg, Judith B. and Pellagatti, Andrea and Bork, Peer and Aloy, Patrick and Gavin, Anne-Claude and Ho, Anthony D.}, title = {Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-06353-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319877}, year = {2018}, abstract = {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.}, language = {en} }