the crystal structure of the dachshund domain of human snon reveals flexibility in the putative protein interaction surface腊肠的晶体结构域的人类平了假定的蛋白质相互作用表面的灵活性.pdfVIP

The Crystal Structure of the Dachshund Domain of Human SnoN Reveals Flexibility in the Putative Protein Interaction Surface 1 . ´ 1. 1 ¨ 3 1 1 Tomas Nyman * , Lionel Tresaugues , Martin Welin , Lari Lehtio , Susanne Flodin , Camilla Persson , 1 ¨ 1 ¨ 1,2 Ida Johansson , Martin Hammarstrom , Par Nordlund * 1 Structural Genomics Consortium, Karolinska Institutet, Stockholm, Sweden, 2 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, ˚ Sweden, 3 Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Turku, Finland Abstract The human SnoN is an oncoprotein that interacts with several transcription-regulatory proteins such as the histone-deacetylase, N-CoR containing co-repressor complex and Smad proteins. This study presents the crystal structure of the Dachshund homology domain of human SnoN. The structure reveals a groove composed of conserved residues with characteristic properties of a protein-interaction surface. A comparison of the 12 monomers in the asymmetric unit reveals the presence of two major conformations: an open conformation with a well accessible groove and a tight conformation with a less accessible groove. The variability in the backbone between the open and the tight conformations matches the differences seen in previously determined structures of individual Dachshund homology domains, suggesting a general plasticity within this fold family. The flexibility observed in the putative protein binding groove may enable SnoN to