title: Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL.
abstract: The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition, and a sequence homologous with the BH3 (Bcl-2 homology 3) domains has recently been identified in the protein, thus making it a potential new member of the BH3-only protein family. In the present study, we provide NMR, SPR (surface plasmon resonance) and crystallographic evidence that a peptide spanning residues 147-172 in SOUL interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL, and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted β-barrel with eight anti-parallel strands and two α-helices. The BH3 domain extends across 15 residues at the end of the second helix and eight amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL.
authors.affiliation: Biocrystallography Laboratory, Department of Biotechnology, University of Verona, Italy.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Ambrosi
authors.forename: Stefano
authors.initials: S
authors.lastname: Capaldi
authors.forename: Michele
authors.initials: M
authors.lastname: Bovi
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Saccomani
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Perduca
authors.forename: Hugo L
authors.initials: HL
authors.lastname: Monaco
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D018360:Crystallography, X-Ray; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D051020:bcl-X Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: C516258:HEBP2 protein, human; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D010455:Peptides; D011257:Pregnancy Proteins; D051020:bcl-X Protein; D006427:Hemin