Structure of the small ubiquitin-like modifier (SUMO)-interacting motif of MBD1-containing chromatin-associated factor 1 bound to SUMO-3.
Post-translational modification by small ubiquitin-like modifier (SUMO) proteins has been implicated in the regulation of a variety of cellular events. The functions of sumoylation are often mediated by downstream effector proteins harboring SUMO-interacting motifs (SIMs) that are composed of a hydrophobic core and a stretch of acidic residues. MBD1-containing chromatin-associated factor 1 (MCAF1), a transcription repressor, interacts with SUMO-2/3 and SUMO-1, with a preference for SUMO-2/3. We used NMR spectroscopy to solve the solution structure of the SIM of MCAF1 bound to SUMO-3. The hydrophobic core of the SIM forms a parallel beta-sheet pairing with strand beta2 of SUMO-3, whereas its C-terminal acidic stretch seems to mediate electrostatic interactions with a surface area formed by basic residues of SUMO-3. The significance of these electrostatic interactions was shown by mutations of both SUMO-3 and MCAF1. The present structural and biochemical data suggest that the acidic stretch of the SIM of MCAF1 plays an important role in the binding to SUMO-3.
Sekiyama
Naotaka
N
Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Ikegami
Takahisa
T
Yamane
Tsutomu
T
Ikeguchi
Mitsunori
M
Uchimura
Yasuhiro
Y
Baba
Daichi
D
Ariyoshi
Mariko
M
Tochio
Hidehito
H
Saitoh
Hisato
H
Shirakawa
Masahiro
M
D020816:Amino Acid Motifs / Q000502:physiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020836:Protein Structure, Quaternary / Q000502:physiology; D012097:Repressor Proteins; D055672:Static Electricity; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C501309:ATF7IP protein, human; D012097:Repressor Proteins; C492189:SUMO3 protein, human; D014157:Transcription Factors; D014452:Ubiquitins