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PDBsum entry 1af3
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Regulatory protein
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PDB id
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1af3
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References listed in PDB file
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Key reference
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Title
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Crystal structure of rat bcl-Xl. Implications for the function of the bcl-2 protein family.
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Authors
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M.Aritomi,
N.Kunishima,
N.Inohara,
Y.Ishibashi,
S.Ohta,
K.Morikawa.
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Ref.
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J Biol Chem, 1997,
272,
27886-27892.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1997,
272,
27886-27892)
copyright 1997.
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