人類轉譯後修飾蛋白(SUMO)聚合鏈與人類環指蛋白4上的多SUMO作用紋區之分子交互作用機制

Molecular Mechanism of Poly-SUMO Chain Recognition by RNF4-SIMs Domain

龔家萱(Chia-Hsuan Kung)

指導教授 ： 黃太煌 ； 余靖

國立清華大學/理學院/化學系/博士(2014年)

摘要

SUMOylation is an important post-translational modification involved in regulating various cellular processes. Similar to ubiquitylation, sumoylation leads to the formation of an isopeptide bond between the C-terminal glycine of SUMO to an acceptor lysine within consensus Ψ-K-x-D/E motif on the target protein. Unlike SUMO1, SUMO2/3 carries a sumoylation motif; thus, similar to ubiquitin, SUMO2/3 can form a poly-SUMO chain. SUMO1 may incorporate in such a chain but as an end cap to terminate further elongation.
Recently, a novel non-covalent interaction mode of SUMO recognition has been identified by means of SIM (SUMO interaction motif), which has a consensus sequence of V/I-x-V/I-V/I. The SIM interacts with SUMO by binding to the groove between second β-strand and α-helix. Interestingly, the E3 ubiquitin-protein ligase RNF4 contains four tandem SIM repeats for selective interaction with poly-SUMO modified proteins, which it targets for ubiquitin-mediated proteasome degradation. Here, a multifaceted biophysical approach, including the usage of NMR, X-Ray crystallography, SAXS and a knowledge-based HADDOCK model, was employed to characterise structures of the RNF4-SIMs domain and tetra-SUMO2 chain to elucidate the interaction between them.

關鍵字

small ubiquitin-like modifier (SUMO) ； SUMO chain ； SUMO interaction motif (SIM) ； RING finger 4 (RNF4) ； nuclear magnetic resonance (NMR) ； small-angle X-ray scattering (SAXS)

參考文獻

1 Schimmel, J., and Vertegaal, A.C.O. (2009) SUMOylation. In:Encyclopedia of Life Sciences (ELS), 1-8

2 Gareau, J. R., and Lima, C.D. (2010) The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nat Rev Mol Cell Biol. 11, 861-871

3 Hay, R. T. (2013) Decoding the SUMO signal. Biochemical Society transactions. 41, 463-473

4 Tatham, M. H., Geoffroy, M. C., Shen, L., Plechanovova, A., Hattersley, N., Jaffray, E. G., Palvimo, J. J. and Hay, R. T. (2008) RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nature cell biology. 10, 538-546

5 Liu, B. and Shuai, K. (2008) Regulation of the sumoylation system in gene expression. Curr Opin Cell Biol. 20, 288-293