title: Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family.
abstract: Bcl-xL is a member of the Bcl-2 protein family, which regulates apoptosis. Preparation of recombinant rat Bcl-xL yielded two forms, one deamidated at -Asn-Gly- sequences to produce isoaspartates and the other not deamidated. The crystal structures of the two forms show that they both adopt an essentially identical backbone structure which resembles the fold of human Bcl-xL: three layers of two alpha-helices each, capped at one end by two short helices. Both forms have a long disordered region, which contains the potential deamidation sites. The molecular structure exhibits a low level of interhelical interactions, the presence of three cavities, and a notable hydrophobic cleft surrounded by walls rich in basic residues. These unique structural features may be favorable for its accommodation into membranes or for possible rearrangement to modulate homo-/heterodimerization. Homology modeling of Bcl-2 and Bax, based on the Bcl-xL structure, suggests that Bax has the strongest potential for membrane insertion. Furthermore, we found a possible interface for interaction with non-Bcl-2 family member proteins, such as CED-4 homologues.
authors.affiliation: Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita-city, Osaka 565, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Aritomi
authors.forename: N
authors.initials: N
authors.lastname: Kunishima
authors.forename: N
authors.initials: N
authors.lastname: Inohara
authors.forename: Y
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D001224:Aspartic Acid