Speaker
Description
The sarcomere is the smallest contractile unit in cardiac and skeletal muscle, where actin and myosin filaments slide past each other to generate tension. This molecular machinery is supported by a subset of highly organised cytoskeletal proteins that perform architectural, mechanical, and signalling functions. Sarcomere ultrastructure is highly organised and delimited by Z-disks, which play a critical role in mechanical stabilisation and force transmission.
In the Z-disks – the lateral boundaries of the sarcomere machinery – the protein α-actinin-2 cross-links antiparallel actin filaments from adjacent sarcomeres, and additionally serves as a binding platform for a number of other Z-disk proteins. In striated muscle cells, the Z-disk represents a highly organized three-dimensional assembly containing a large directory of proteins orchestrated in a multi-protein complex centred on its major component α-actinin, with still poorly understood hierarchy and three-dimensional interaction map. To investigate the molecular structural architecture of the Z-disk, the assembly hierarchy, and structure-function relationships, we are employing an integrative structural biology strategy that combines molecular biophysics, structural, and biochemical approaches.
FATZ proteins interact with α-actinin and five other core Z-disk proteins, contributing to the assembly and maintenance of myofibrils as a hub for protein interactions. I will present our studies on the interaction of the major Z-disk protein α-actinin-2 with FATZ-1 and Z-portion of titin, forming dynamic fuzzy complexes, and discuss findings in view of asymmetric sorting of α-actinin and sarcomeric Z-disk architecture and assembly.
Furthermore, our recent discover that FATZ-1 can phase-separate and form biomolecular condensates with α-actinin-2 and other three Z-disk proteins raises the intriguing question of whether FATZ proteins can create an interaction hub for Z-disk proteins during myofibrillogenesis via membrane-less compartmentalization.
| Select Topic 1 | Modern Methods in Structural Biology and Dynamics |
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