Change search
ReferencesLink to record
Permanent link

Direct link
Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Show others and affiliations
2008 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 582, no 25-26, 3590-3594 p.Article in journal (Refereed) Published
Abstract [en]

Evasion of apoptosis is recognized as a characteristic of malignant growth. Anti-apoptotic B-cell lymphoma-2 (Bcl-2) family members have therefore emerged as potential therapeutic targets due to their critical role in proliferating cancer cells. Here, we present the crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim. The structure reveals distinct features at the peptide-binding site, likely to define the binding specificity for pro-apoptotic proteins. Superposition of the Bfl-1:Bim complex with that of Mcl-1:Bim reveals a significant local plasticity of hydrophobic interactions contributed by the Bim peptide, likely to be the basis for the multi specificity of Bim for anti-apoptotic proteins.

Place, publisher, year, edition, pages
2008. Vol. 582, no 25-26, 3590-3594 p.
Keyword [en]
Apoptosis, B-cell lymphoma-2, Cancer, Bfl-1; A1, Crystal structure
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-25483DOI: 10.1016/j.febslet.2008.09.028ISI: 000260807500004OAI: diva2:199816
Available from: 2008-09-22 Created: 2008-09-22 Last updated: 2012-02-13Bibliographically approved
In thesis
1. Structural studies of proteins in apoptosis and lipid signaling
Open this publication in new window or tab >>Structural studies of proteins in apoptosis and lipid signaling
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Signaling pathways control the fate of the cell. For example, they promote cell survival or commit the cell to death (apoptosis) in response to cell injury or developmental stimuli, decisions, which are vital for the proper development and functioning of metazoan. Tight control of such pathways is essential; dysregulation of apoptosis can disrupt the delicate balance between cell proliferation and cell death ending up in pathological processes, including cancer, autoimmunity diseases, inflammatory diseases, or degenerative disorders. We have used a structural genomic approach to study the structure and function of key proteins involved in apoptosis and lipid signaling: the antiapoptotic Bcl-2 family member Bfl-1 in complex with a Bim peptide, the BIR domains of the Inhibitor of Apoptosis (IAP) family members, cIAP2 and NAIP and the a lipid kinase YegS. The structural analysis of the apoptosis regulatory proteins has revealed important information on the structural determinants for recognition of interacting proteins, which can now assist in the development of therapeutic drugs for human diseases. The structural and complementing biochemical studies of the lipid kinase YegS have reveled the first detailed information on a lipid kinase and explained important aspects of its structure-function relationship.

Finally, one subject of this work aim to solve what is arguably the most challenging problem in structural projects – to obtain a high production level of proteins suitable for structural studies. We have developed a highthroughput protein solubility screening, the colony filtration (CoFi) blot, which allows soluble clones to be identified from large libraries of protein variants and now constitute a powerful tool for solving difficult protein production problems.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik, 2008. 74 p.
proteins, crystal structure, apoptosis, cancer, CoFi-Blot, kinases, lipid signaling
National Category
Structural Biology
Research subject
Structural Biology
urn:nbn:se:su:diva-8212 (URN)978-91-7155-703-2 (ISBN)
Public defence
2008-09-11, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00 (English)
Available from: 2008-09-22 Created: 2008-09-22 Last updated: 2010-01-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Herman, Maria Dolores
By organisation
Department of Biochemistry and Biophysics
In the same journal
FEBS Letters
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 31 hits
ReferencesLink to record
Permanent link

Direct link