Publications by authors named "Dirk Dedden"
RAF protein kinases are essential effectors in the MAPK pathway and are important cancer drug targets. Structural understanding of RAF activation is so far based on cryo-electron microscopy (cryo-EM) and X-ray structures of BRAF in different conformational states as inactive or active complexes with KRAS, 14-3-3 and MEK1. In this study, we have solved the first cryo-EM structures of CRAF/14-3-3 at 3.
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- Integrin αβ is an essential receptor for fibronectin that plays a significant role in cell migration, but the mechanisms behind its conformational changes during this process remain unclear.
- Recent cryo-electron microscopy studies provided detailed structures of native human αβ with fibronectin, revealing complex interactions and a newly identified binding site that helps stabilize the integrin's opening.
- The findings challenge traditional views about integrin conformation and ligand affinity, showing that the presence of manganese ions increases binding strength even in a less bent state, suggesting that ligand binding drives the opening of integrins rather than the conformation itself.
Focal adhesions (FA) are large macromolecular assemblies which help transmit mechanical forces and regulatory signals between the extracellular matrix and an interacting cell. Two key proteins talin and vinculin connecting integrin to actomyosin networks in the cell. Both proteins bind to F-actin and each other, providing a foundation for network formation within FAs.
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- Focal adhesions (FAs) are important for cell functions like adhesion and movement, with talin being a key protein that links integrins to the cytoskeleton.
- Researchers used cryoelectron microscopy to explore the structure of talin1, finding it has a self-inhibiting mechanism that prevents integrin activation when needed.
- The study shows that talin can switch between a compact form and a longer, active conformation, which is essential for regulating cell adhesion and signaling processes.
Eukaryotic cells can direct secretion to defined regions of their plasma membrane. These regions are distinguished by an elaborate architecture of proteins and lipids that are specialized to capture and fuse post-Golgi vesicles. Here, we show that the proteins Boi1p and Boi2p are important elements of this area of active exocytosis at the tip of growing yeast cells.
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- Integrin-based adhesions are essential for cell migration, with talin acting as a molecular clutch that connects integrins to the actomyosin cytoskeleton.
- The Kank protein family is identified as novel components of focal adhesions, accumulating at specific regions and binding to talin to enhance its activation.
- Kank proteins reduce the strength of the integrin-talin connection to the actomyosin, leading to decreased cell migration speed by promoting slippage in adhesion complexes.