Author:
Szaniszló Tamás,Fülöp Máté,Pajkos Mátyás,Erdős Gábor,Kovács Réka Ágnes,Vadászi Henrietta,Kardos József,Dosztányi Zsuzsanna
Abstract
AbstractDynein light chain LC8 is a small dimeric hub protein that recognizes its partners through short linear motifs and is commonly assumed to drive their dimerization. It has more than 100 known binding partners involved in a wide range of cellular processes. Recent large-scale interaction studies suggested that LC8 could also play a role in the ciliary/centrosome system. However, the cellular function of LC8 in this system remains elusive. In this work, we characterized the interaction of LC8 with the centrosomal protein lebercilin (LCA5), which is associated with a specific form of ciliopathy. We showed that LCA5 binds LC8 through two linear motifs. In contrast to the commonly accepted model, LCA5 forms dimers through extensive coiled coil formation in a LC8-independent manner. However, LC8 enhances the oligomerization ability of LCA5 that requires a finely balanced interplay of coiled coil segments and both binding motifs. Based on our results, we propose that LC8 acts as an oligomerization engine that is responsible for the higher order oligomer formation of LCA5. As LCA5 shares several common features with other centrosomal proteins, the presented LC8 driven oligomerization could be widespread among centrosomal proteins, highlighting an important novel cellular function of LC8.
Funder
ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology
National Research, Development and Innovation Fund of Hungary
Eötvös Loránd University
Publisher
Springer Science and Business Media LLC
Reference48 articles.
1. Ekman, D., Light, S., Björklund, A. K. & Elofsson, A. What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae?. Genome Biol. 7, R45 (2006).
2. Hu, G., Wu, Z., Uversky, V. N. & Kurgan, L. Functional analysis of human hub proteins and their interactors involved in the intrinsic disorder-enriched interactions. Int. J. Mol. Sci. 18, 12 (2017).
3. Chang, X., Xu, T., Li, Y. & Wang, K. Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of ‘date’ and ‘party’ hubs. Sci. Rep. 3, 1691 (2013).
4. Liang, J., Jaffrey, S. R., Guo, W., Snyder, S. H. & Clardy, J. Structure of the PIN/LC8 dimer with a bound peptide. Nat. Struct. Biol. 6, 735–740 (1999).
5. Singh, G. P., Ganapathi, M. & Dash, D. Role of intrinsic disorder in transient interactions of hub proteins. Proteins 66, 761–765 (2007).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献