HEИндивидуална стипендия2022–2024

PomXYZ · The PomXYZ cluster in the bacterium Myxococcus xanthus: Self-assembly, translocation, and fission of an active protein complex that guides cell division

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-10-01 → 2024-09-30
Финансиране от ЕС: 189 687 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Протеините PomX, PomY и PomZ при бактерията Myxococcus xanthus се обединяват в комплекс, който определя мястото на клетъчното делене. Разбирането на този механизъм помага да се разбере как клетките организират вътрешните си структури, за да се размножават правилно.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

The PomXYZ cluster in the bacterium Myxococcus xanthus: Self-assembly, translocation, and fission of an active protein complex that guides cell division

Subcellular self-organization is fundamentally necessary for cellular life, and in particular for cell division. There, the future cell division site at midcell needs to be marked for the cell division machinery. In the rod-shaped bacterium Myxococcus xanthus, the proteins PomX, PomY, and PomZ play a key role in this process. These proteins self-assemble to form a protein cluster on the cell nucleoid. Driven by a non-equilibrium reaction cycle of PomZ, the cluster then localizes at the cell midpoint, where it recruits the cell-division machinery. Upon division of the cell, also the cluster divides; on each of the respective daughter cells, the cluster then in turn translocates to the cell midpoint to again mark the cell division site. A key aspect of the cluster translocation mechanism is the coupling of spatial dynamics with reactions. More specifically, PomZ proteins can exist in either an activated (dimeric, ATP-bound) state or a deactivated (monomeric) state. In the absence of PomX/PomY, PomZ is preferably in its activated form; the presence of PomX stimulates the deactivation of PomZ, whereby the bound ATP is hydrolized to ADP; the resulting PomZ monomers then diffusive in the cytosol, where after some time they again form ATP-bound dimers. This reaction cycle consumes energy, and the interaction of the ATP-bound PomZ dimers with the PomX/PomY cluster generates an effective force that drives the cluster towards midcell. The objective of the project was to develop and study a mesoscopic model for the cell cycle of M. xanthus, and in particular to quantify the constraints imposed on the properties and interactions of the participating proteins. To account for the non-equilibrium PomZ reaction cycle described in the previous paragraph, the coupling of spatial dynamics with reactions is a key feature of our modeling. More explicitly, we consider overdamped stochastic dynamics of particles that can change their internal state (i.e. interaction properties) via reactions; to include the possibility of locally stimulated reactions, the reaction rates can depend on the local neighborhood of a particle. Therefore, in this particle-based reaction-diffusion model, both the spatial dynamics depends on the internal state of a particle, and the reaction rates at which the internal state changes depend on the spatial configuration.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

In my research project I will theoretically model a fundamental process in the cell division of the model bacterium Myxococcus xanthus, namely the process for guiding the machinery for cell division to midcell. In M. xanthus, a cluster comprised of the proteins PomX, PomY, PomZ self-assembles on the nucleoid surface and in an ATP-consuming reaction cycle translocates to midcell, to guide the cell division machinery there. During cell division the Pom cluster undergoes fission, and the resulting two Pom clusters on the daughter cells again translocate to the respective midcell to induce further cell divisions. I will consider a mesoscopic model which combines spatial dynamics with locally stimulated reactions, to study the formation, translocation, and fission of the Pom cluster. My model is informed, and will be further refined, using experimental results of the group of Lotte Sgaard-Andersen at the MPI for Terrestrial Microbiology, an established collaborator of my supervisor Erwin Frey. I will quantify the constraints imposed on the protein-protein and protein-nucleoid interactions by the tasks the Pom cluster needs to fulfill (self-assembly, translocation, fission), and relate my mesoscopic model both to previously proposed heuristic models on Pom cluster translocation and to (stochastic) reaction-diffusion models. My project will lead to a deeper understanding of how biological systems actively create and maintain order. My mesoscopic model combines spatial dynamics with locally stimulated reactions, which are the two conceptual building blocks needed for spatial organization driven by energy consumption. My model will therefore be applicable also in other instances of biological self-organization, as well as in self-assembly of artificial nanostructures, both of which are active and growing research directions. My project will therefore make my research profile more impactful, which will help me to reach my goal of becoming an independent group leader.

Оригинален текст от CORDIS (на английски).

Участници

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggКоординаторГермания