6bf2

From Proteopedia

(Difference between revisions)

Revision as of 09:52, 4 December 2019

Solution structure of a Bcl-xL S62E mutant

Structural highlights

6bf2 is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 5l1y. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	BCL2L1, BCL2L, BCLX (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2CL1_HUMAN] 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] Isoform Bcl-X(S) promotes apoptosis.^[3] ^[4]

Publication Abstract from PubMed

Intrinsically disordered regions (IDRs) of proteins often regulate function upon post-translational modification (PTM) through interactions with folded domains. An IDR linking two alpha-helices (alpha1-alpha2) of the antiapoptotic protein Bcl-xL experiences several PTMs that reduce antiapoptotic activity. Here, we report that PTMs within the alpha1-alpha2 IDR promote its interaction with the folded core of Bcl-xL that inhibits the proapoptotic activity of two types of regulatory targets, BH3-only proteins and p53. This autoregulation utilizes an allosteric pathway whereby, in one direction, the IDR induces a direct displacement of p53 from Bcl-xL coupled to allosteric displacement of simultaneously bound BH3-only partners. This pathway operates in the opposite direction when the BH3-only protein PUMA binds to the BH3 binding groove of Bcl-xL, directly displacing other bound BH3-only proteins, and allosterically remodels the distal site, displacing p53. Our findings show how an IDR enhances functional versatility through PTM-dependent allosteric regulation of a folded protein domain.

Regulation of apoptosis by an intrinsically disordered region of Bcl-xL.,Follis AV, Llambi F, Kalkavan H, Yao Y, Phillips AH, Park CG, Marassi FM, Green DR, Kriwacki RW Nat Chem Biol. 2018 Mar 5. pii: 10.1038/s41589-018-0011-x. doi:, 10.1038/s41589-018-0011-x. PMID:29507390^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Follis AV, Llambi F, Kalkavan H, Yao Y, Phillips AH, Park CG, Marassi FM, Green DR, Kriwacki RW. Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nat Chem Biol. 2018 Mar 5. pii: 10.1038/s41589-018-0011-x. doi:, 10.1038/s41589-018-0011-x. PMID:29507390 doi:http://dx.doi.org/10.1038/s41589-018-0011-x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6bf2"

@@ Line 1: / Line 1: @@
 ==Solution structure of a Bcl-xL S62E mutant==
-<StructureSection load='6bf2' size='340' side='right' caption='[[6bf2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='6bf2' size='340' side='right'caption='[[6bf2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6bf2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5l1y 5l1y]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BF2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BF2 FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 ==See Also==
-*[[B-cell lymphoma protein|B-cell lymphoma protein]]
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Follis, A Viacava]]
 [[Category: Kriwacki, R W]]
 [[Category: Phillips, A]]
 [[Category: Apoptosis]]

6bf2

From Proteopedia

Revision as of 09:52, 4 December 2019

Solution structure of a Bcl-xL S62E mutant

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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