| Structural highlights
Function
[B2CL1_RAT] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family.,Aritomi M, Kunishima N, Inohara N, Ishibashi Y, Ohta S, Morikawa K J Biol Chem. 1997 Oct 31;272(44):27886-92. PMID:9346936[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shiraiwa N, Inohara N, Okada S, Yuzaki M, Shoji S, Ohta S. An additional form of rat Bcl-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells. J Biol Chem. 1996 May 31;271(22):13258-65. PMID:8662675
- ↑ Tilly JL, Tilly KI, Kenton ML, Johnson AL. Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels. Endocrinology. 1995 Jan;136(1):232-41. PMID:7828536
- ↑ Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, Bossy-Wetzel E, Bennett MV, Pypaert M, Hickman JA, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2169-74. doi:, 10.1073/pnas.0711647105. Epub 2008 Feb 4. PMID:18250306 doi:http://dx.doi.org/10.1073/pnas.0711647105
- ↑ Aritomi M, Kunishima N, Inohara N, Ishibashi Y, Ohta S, Morikawa K. Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family. J Biol Chem. 1997 Oct 31;272(44):27886-92. PMID:9346936
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