| Structural highlights
Disease
SUMO1_HUMAN Defects in SUMO1 are the cause of non-syndromic orofacial cleft type 10 (OFC10) [MIM:613705; also called non-syndromic cleft lip with or without cleft palate 10. OFC10 is a birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=A chromosomal aberation involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.[1]
Function
SUMO1_HUMAN Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development.[2] [3] [4] [5]
Publication Abstract from PubMed
PML and several other proteins localizing in PML-nuclear bodies (PML-NB) contain phosphoSIMs (SUMO-interacting motifs), and phosphorylation of this motif plays a key role in their interaction with SUMO family proteins. We examined the role that phosphorylation plays in the binding of the phosphoSIMs of PML and Daxx to SUMO1 at the atomic level. The crystal structures of SUMO1 bound to unphosphorylated and tetraphosphorylated PML-SIM peptides indicate that three phosphoserines directly contact specific positively charged residues of SUMO1. Surprisingly, the crystal structure of SUMO1 bound to a diphosphorylated Daxx-SIM peptide indicate that the hydrophobic residues of the phosphoSIM bind in a manner similar to that seen with PML, but important differences are observed when comparing the phosphorylated residues. Together, the results provide an atomic level description of how specific acetylation patterns within different SUMO family proteins can work together with phosphorylation of phosphoSIM's regions of target proteins to regulate binding specificity.
Structural and Functional Characterization of the Phosphorylation-Dependent Interaction between PML and SUMO1.,Cappadocia L, Mascle XH, Bourdeau V, Tremblay-Belzile S, Chaker-Margot M, Lussier-Price M, Wada J, Sakaguchi K, Aubry M, Ferbeyre G, Omichinski JG Structure. 2014 Dec 11. pii: S0969-2126(14)00360-8. doi:, 10.1016/j.str.2014.10.015. PMID:25497731[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Alkuraya FS, Saadi I, Lund JJ, Turbe-Doan A, Morton CC, Maas RL. SUMO1 haploinsufficiency leads to cleft lip and palate. Science. 2006 Sep 22;313(5794):1751. PMID:16990542 doi:10.1126/science.1128406
- ↑ Mahajan R, Delphin C, Guan T, Gerace L, Melchior F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell. 1997 Jan 10;88(1):97-107. PMID:9019411
- ↑ Kamitani T, Nguyen HP, Yeh ET. Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem. 1997 May 30;272(22):14001-4. PMID:9162015
- ↑ Meulmeester E, Kunze M, Hsiao HH, Urlaub H, Melchior F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol Cell. 2008 Jun 6;30(5):610-9. doi: 10.1016/j.molcel.2008.03.021. PMID:18538659 doi:10.1016/j.molcel.2008.03.021
- ↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
- ↑ Cappadocia L, Mascle XH, Bourdeau V, Tremblay-Belzile S, Chaker-Margot M, Lussier-Price M, Wada J, Sakaguchi K, Aubry M, Ferbeyre G, Omichinski JG. Structural and Functional Characterization of the Phosphorylation-Dependent Interaction between PML and SUMO1. Structure. 2014 Dec 11. pii: S0969-2126(14)00360-8. doi:, 10.1016/j.str.2014.10.015. PMID:25497731 doi:http://dx.doi.org/10.1016/j.str.2014.10.015
|
