Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex Journal Article
| Authors: | Duan, X.; Sarangi, P.; Liu, X.; Rangi, G. K.; Zhao, X.; Ye, H. |
| Article Title: | Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex |
| Abstract: | The Smc5/6 complex is an evolutionarily conserved chromosomal ATPase required for cell growth and DNA repair. Its Mms21 subunit supports both functions by docking to the arm region of Smc5 and providing SUMO ligase activity. Here, we report the crystal structure of Mms21 in complex with the Smc5 arm. Our structure revealed two distinct structural and functional domains of the Smc5-bound Mms21: its N-terminal half is dedicated to Smc5 binding by forming a helix bundle with a coiled-coil structure of Smc5; its C-terminal half includes the SUMO ligase domain, which adopts a new type of RING E3 structure. Mutagenesis and structural analyses showed that the Mms21-Smc5 interface is required for cell growth and resistance to DNA damage, while the unique Mms21 RING domain confers specificity to the SUMO E2-E3 interaction. Through structure-based dissection of Mms21 functions, our studies establish a framework for understanding its roles in the Smc5/6 complex. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; mutation; nonhuman; protein conformation; protein function; proteins; animals; cell cycle proteins; dna damage; cell growth; carboxy terminal sequence; structure-activity relationship; dna; amino acid sequence; molecular sequence data; amino terminal sequence; saccharomyces cerevisiae; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; multiprotein complexes; binding sites; rats; saccharomyces cerevisiae proteins; protein subunit; molecular docking; structure analysis; ubiquitin protein ligase e3; enzyme specificity; adenosine triphosphatase; mms21 protein; smc5 complex; smc6 complex; sumo protein; enzyme binding; enzyme structure; enzyme substrate complex; enzyme subunit; ring finger motif; site directed mutagenesis; sumoylation; sumo-1 protein; ubiquitin-activating enzymes; ubiquitin-conjugating enzymes |
| Journal Title: | Molecular Cell |
| Volume: | 35 |
| Issue: | 5 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2009-09-11 |
| Start Page: | 657 |
| End Page: | 668 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2009.06.032 |
| PUBMED: | 19748359 |
| PROVIDER: | scopus |
| PMCID: | PMC2993495 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: MOCEF" - "Source: Scopus" |
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