PDBsum entry 1af3

Regulatory protein

PDB id: 1af3

Contents

Protein chain

145 a.a. *

Waters ×51

* Residue conservation analysis

PDB id:

1af3

Name:

Regulatory protein

Title:

Rat bcl-xl an apoptosis inhibitory protein

Structure:

Apoptosis regulator bcl-x. Chain: a. Fragment: soluble region. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.50Å R-factor: 0.225 R-free: 0.273

Authors:

M.Aritomi,N.Kunishima,N.Inohara,Y.Ishibashi,S.Ohta,K.Morikawa

Key ref:

M.Aritomi et al. (1997). Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family. J Biol Chem, 272, 27886-27892. PubMed id: 9346936 DOI: 10.1074/jbc.272.44.27886

Date:

21-Mar-97 Release date: 07-Jul-97

Protein chain

P53563  (B2CL1_RAT) -  Bcl-2-like protein 1 from Rattus norvegicus

Seq: 233 a.a.

Struc: 145 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.272.44.27886

J Biol Chem 272:27886-27892 (1997)

PubMed id: 9346936

Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family.

M.Aritomi, N.Kunishima, N.Inohara, Y.Ishibashi, S.Ohta, K.Morikawa.

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.

Selected figure(s)

Figure 3.
Fig. 3. Stereoview of the three cavities and the -carbon backbone. Cavities were calculated by the GRASP (42) program. The^ view is from the bottom looking into helices 5 and 6. Cavity A is formed by Phe^12, Leu90, Ala^93, Gly94, Phe^97, Trp137, Ile^140, Val141, Ala^142, Phe^144, Ser145, Trp181, Ile^182, Trp188, Phe^191, and Tyr195; cavity B by Phe^12, Leu13, Lys16, Leu17, Lys20, Tyr22, Gly148, Cys151, and Val152; and cavity C by Leu112, Ile^114, Thr115, Pro116, Gly117, Thr118, Phe^123, Leu150, Ser154, Leu162, Arg165, Ile^166, and Trp169. Cavities A and B are partitioned by the side chain of Phe^12.

Figure 4.
Fig. 4. Stereo pairs showing the hydrophobic clefts in the bottom region for Bcl-x[L](B) (a) and for a Bax model (b). The hydrophobicity was mapped onto the solvent accessible surface using the GRASP (42) program, with the hydropathy values (44). The molecules are viewed in the same direction as in Fig. 3. The blue color represents hydrophilic regions and the yellow represents hydrophobic^ regions. The two red lines in a indicate the hydrogen-bonds: Tyr22-Asp156 and Arg165-Pro116. The three-dimensional structure of Bax was constructed by homology modeling based on that of Bcl-x[L](B) and by using a previously reported sequence alignment (29).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1997, 272, 27886-27892) copyright 1997.

Figures were selected by an automated process.