Structural modeling of histone methyltransferase complex Set1C from Saccharomyces cerevisiae using constraint-based docking
PROTEOMICS
Authors: Tuukkanen, Anne; Huang, Bingding; Henschel, Andreas; Stewart, Francis; Schroeder, Michael
Abstract
Set1C is a histone methyltransferase playing an important role in yeast gene regulation Modeling the structure of this eight subunit protein complex is an important open problem to further elucidate its functional mechanism Recently, there has been progress in modeling of larger complexes using constraints to restrict the combinatorial explosion in binary docking of subunits Here we model the subunits of Set1C and develop a constraint based docking approach which uses high quality protein interaction as well as functional data to guide and constrain the combinatonal assembly procedure We obtained 22 final models The core complex consisting of the subunits Set1 Bre2 Sdc1 and Swd2 is conformationally conserved in over half of the models thus giving high confidence We characterize these high confidence and the lower confidence interfaces and discuss implications for the function of Set1C
Integrated physical map of the human essential tremor gene region (ETM2) on chromosome 2p24.3-p24.2
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Authors: Higgins, JJ; Lombardi, RQ; Pucilowska, J; Ruszczyk, MU
Abstract
A gene for autosomal dominant familial essential tremor maps to a 9.1 cM interval flanked by loci D2S224 and D2S405 (ETM2) on human chromosome 2p24.3-p24.2. The recombinatorial boundaries of the interval were refined on a radiation hybrid map to a 123 cR minimal critical region (MCR) between D2S224 and D2S2221. High-throughput non-isotopic screening of bacterial artificial chromosomes (BACs) was used to assemble a physical map of the region. A scaffold BAC map of 31 overlapping clones was ordered by their sequence tagged site (STS) content using PCR and Southern blotting. A complementary 3.9 Mb integrated physical map of the human ETM2 region was constructed by identifying GenBank contigs that contained seven BAC DNA sequences and common STSs. Thirty-three transcripts including five known genes (MATN3, LAPTM4A, SDC1, PUM2, and APOB) were identified in the MCR and ordered on an integrated contig by PCR and virtual mapping. This physical map will provide a template for genomic sequencing and the identification of a gene for essential tremor. (C) 2003 Wiley-Liss, Inc.