1G5J

COMPLEX OF BCL-XL WITH PEPTIDE FROM BAD

Summary for 1G5J

• Entry DOI: 10.2210/pdb1g5j/pdb
• Related: 1BXL 1G5M 1G5O
• Descriptor: APOPTOSIS REGULATOR BCL-X, BAD PROTEIN (2 entities in total)
• Functional Keywords: complex, apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion membrane; Single-pass membrane protein (By similarity): Q07817; Mitochondrion outer membrane: Q92934
• Total number of polymer chains: 2
• Total formula weight: 23085.56

Authors

Petros, A.M.,Nettesheim, D.G.,Wang, Y.,Olejniczak, E.T.,Meadows, R.P.,Mack, J.,Swift, K.,Matayoshi, E.D.,Zhang, H.,Thompson, C.B.,Fesik, S.W. (deposition date: 2000-11-01, release date: 2001-02-07, Last modification date: 2024-05-22)

Primary citation

Petros, A.M.,Nettesheim, D.G.,Wang, Y.,Olejniczak, E.T.,Meadows, R.P.,Mack, J.,Swift, K.,Matayoshi, E.D.,Zhang, H.,Thompson, C.B.,Fesik, S.W.
Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies.
Protein Sci., 9:2528-2534, 2000

PubMed Abstract: The three-dimensional structure of the anti-apoptotic protein Bcl-xL complexed to a 25-residue peptide from the death promoting region of Bad was determined using NMR spectroscopy. Although the overall structure is similar to Bcl-xL bound to a 16-residue peptide from the Bak protein (Sattler et al., 1997), the Bad peptide forms additional interactions with Bcl-xL. However, based upon site-directed mutagenesis experiments, these additional contacts do not account for the increased affinity of the Bad 25-mer for Bcl-xL compared to the Bad 16-mer. Rather, the increased helix propensity of the Bad 25-mer is primarily responsible for its greater affinity for Bcl-xL. Based on this observation, a pair of 16-residue peptides were designed and synthesized that were predicted to have a high helix propensity while maintaining the interactions important for complexation with Bcl-xL. Both peptides showed an increase in helix propensity compared to the wild-type and exhibited an enhanced affinity for Bcl-xL.

PubMed: 11206074
DOI: 10.1017/S096183680000331X

Experimental method

SOLUTION NMR