B-cell lymphoma protein

From Proteopedia

Revision as of 10:03, 27 February 2018

spinqualitylabelsall models NMR structure of bcl-2 1g5m Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image B-cell lymphoma proteins (Bcl) family are pro-survival proteins. Bcl-2 and Bcl-xL suppress cell death and Bak and Bax promote apoptosis.Bcl-xL (Bcl-2-like protein 1) known as survival protein is the regulator of apoptosis. Mcl-1 is an induced myeloid cell leukemia differentiation protein. Bcl-2-like-7 is called Bak for Bcl-2 homologous antagonist/killer. Bcl-2-like-4 is called Bax. Bcl-2-like-11 is called Bim. BH3 domain is a Bcl-2 homology 3 domain present in Bcl-2 protein family. Contents 1 Overview 2 Cancer 3 Experiment 4 Conclusions Overview Bcl-2 is a family of genes and proteins that govern the mitochondrial membrane permeabilization (MMP). Bcl-2 derives its name from B-cell lymphoma 2 which came from being the second member of a range of proteins initially described as a reciprocal gene translocation in chromosomes 14 and 18 in follicular lymphomas. The genes and proteins can be either pro-apoptotic (Bax, BAD, Bak and Bok) or anti-apoptotic (Bcl-2, Bcl-xL, and Bcl-w). These genes interact with the Bcl-2 protein structure, which result in either a pro- or anti-apoptosis function. The sites on Bcl-2 where the genes interact, have been characterized by Dr. JC Reed et al[2]. These domains are , , and . Dr. Reed found that any deletion of these domains, abolishes Bcl-2's ability to suppress cell death. Apoptosis is the programmed death of cells. It is central to the development and homeostasis of multicellular organisms, and it is the route by which unwanted or harmful cells are eliminated from the organism. The mitochondria is a large contributor in the subcellular partitioning of the apoptotic activator molecules such as cytochrome c. There are several triggering agents such as Ca2+, reactive oxygen species, certain lipid molecules and certain protein kinases that can induce MMP. The interaction opens the protein permeable pores that allow the release of several proteins including cytochrome c, Smac/Diablo, AIF, Endonuclease G, etc. Depending on their activated function, Bcl-2 either promotes the release or sequesters the function of the specific proteins. See also Fragment-Based Drug Discovery. Cancer Bcl-2 is involved in a number of cancers. These include melanoma, breast, prostate, and lung carcinomas. It is also known to have involvement in schizophrenia as well as autoimmunity. Experiment Research from Dr. Mee Young Hong, et al has shown that dietary fish oil is protective against colon tumorigenesis[1]. However the mechanism by which this regulation is taking place is not well understood. Dr. Hong’s group hypothesized that dietary fish oil increases apoptosis by down regulating bcl-2 expression. Rat tissues were prepared by acclimating the rats for 1 week, providing an experimental diet for 2 weeks and injecting the rats with a colon carcinogen and then terminating the rats at 3, 6, 9 and 12 hours later. The experimental diets only differed in the fat composition. The first diet used corn oil while the second diet used fish oil. The main constitutional differences between the two oils were significantly higher amounts of EPA and DHA in the fish oil compared to the corn oil and higher concentration of n-6 in the corn oil. The corn oil was also chosen because it contains linoleic acid, which is known to promote colon tumorigenesis. Bcl-2 was analyzed using quantitative immunohistochemistry (IHC) and also immunoblot analysis. IHC is the process of localizing proteins in tissues by exploiting the principle of antibodies binding specifically to antigens. The visualization of the antibody is commonly accomplished by conjugating an enzyme to the antibody. This can produce a color changing reaction. The advantage of this method is the ability to show exactly where a given protein is located. Twenty column crypts were analyzed for each animal. The images of the crypts were visualized using a light microscope, captured on a digital camera and analyzed using NIH software. Conclusions Bcl-2 decreases in expression until 9h post carcinogenic injection in both the proximal and distal colon. This corresponds to an apoptotic index peak at 9h in both the proximal and distal colon. Fish oil feeding resulted in lower levels of bcl-2 at the upper third of the crypt in the distal colon compared with corn oil feeding. Fish oil feeding doubled the apoptotic index compared with corn oil feeding in the upper third crypts in the distal colon.

3D structures of Bcl-2

Updated on 27-February-2018 {{#tree:id=OrganizedByTopic|openlevels=0|

• Bcl-xL (Bcl-2-like protein 1)

• • 1maz, 1r2d, 2b48, 4ppi – hBcl-xL – human
    
  • 1r2e, 1r2g, 1r2h, 1r2i, 3cva - hBcl-xL (mutant)
    
  • 2lpc, 2m03, 2me8, 2me9, 1lxl - hBcl-xL – NMR
    
  • 6bf2 - hBcl-xL (mutant) – NMR
    
  • 3fdm - hBcl-xL + α/β peptide foldamer
    
  • 2mej - hBcl-xL + p53 - NMR
    
  • 3inq - hBcl-xL (mutant) + inhibitor
    
  • 1ysg, 3sp7, 3spf, 3wiz, 4tuh, 3zln, 3zk6, 3zlo, 3zlr, 4c52, 4c5d, 2yxj, 4qnq, 4qvx - hBcl-xL + inhibitor
    
  • 2w3l – hBcl-xL + quinoline derivative
    
  • 2o1y, 2o2m, 2o2n, 1ysi, 1ysn, 2o21, 2o22, 2o2f - hBcl-xL + sulfonamide derivative – NMR
    
  • 3qkd, 4ehr - hBcl-xL + sulfonamide derivative
    
  • 2pon - hBcl-xL + Beclin-1- NMR
    
  • 2p1l - hBcl-xL (mutant) + Beclin-1
    
  • 3ihc, 3iih, 1pq0 – mBcl-xL residues 1-196 – mouse
    
  • 3ihd, 3ihe, 3ihf, 3iig, 3ilb, 3ilc - mBcl-xL residues 1-196 (mutant)
    
  • 2bzw - mBcl-xL residues 1-211 + BAD
    
  • 1pq1, 5c3g - mBcl-xL residues 1-196 + BIM peptide
    
  • 1af3 - rBcl-xL soluble domain
    
  • 1bxl - Bcl-xL + Bak peptide – Escherichia coli – NMR
    
  • 5twa - Bcl-xL + Bak peptide – sponge
    

• Bcl-xL complex with BH3 domain peptide

• • 3pl7 - hBcl-xL (mutant) + apoptosis regulator BAX BH3 domain
    
  • 5fmk, 5fmj - hBcl-xL + Bak BH3 domain
    
  • 4qve - hBcl-xL + BID BH3 domain
    
  • 1g5j - hBcl-xL + BAD BH3 peptide
    
  • 5b1z - hBcl-xL + BHX BH3 domain
    
  • 4z9v - hBcl-xL + TCTP BH3 domain
    
  • 2yq6, 4qvf, 4yk9, 3fdl, 5agx, 4yj4, 3io8, 2yq7, 5vx3, 5agw - hBcl-xL + BIM BH3 domain
    
  • 2yj1, 4bpk, 4hnj - hBcl-xL + α/β-Puma BH3 domain
    
  • 4a1u, 4a1w - hBcl-xL + α/β-foldamer BH3 domain
    
  • 3r85 - hBcl-xL + heme-binding protein BH3 peptide
    
  • 2lp8 – hBcl-xL + Bcl-2 homologous antagonist/killer BH3 peptide - NMR
    
  • 2m04 – hBcl-xL (mutant) + Bcl-2 binding component 3 BH3 peptide - NMR
    
  • 5wos - Bcl-xL + hBIM BH3 domain – canarypox virus
    
  • 5tzp - fpvBcl-xL + BIK BH3 domain – fowlpox virus
    
  • 5tzq - fpvBcl-xL + Bmf BH3 domain
    

• Bcl-2

• • [[1gjh, 1g5m – hBcl-2
    
  • 4aq3, 4man, 5jsn, 4ieh – hBcl-2 + inhibitor
    
  • 4lvt, 4lxd – hBcl-2 (mutant) + inhibitor
    
  • 5fcg – hBcl-2 (mutant) + HBX BH3 domain
    
  • 2xa0 – hBcl-2 residues 1-207 + apoptosis regulator Bax BH3 domain
    
  • 2o21, 2o22, 2o2f, 1ysw - hBcl-2 + sulfonamide derivative – NMR

• Bcl-2-related protein A1 (Bfl-1)

• • 5whi - hBcl-2A1 (mutant)
    
  • 2vm6 – hBcl-2A1 + hBIM BH3 peptide
    
  • 2vof - mBcl-2A1 + Bcl-2 binding component 3 BH3 peptide
    
  • 2vog - mBcl-2A1 + Bmf BH3 peptide
    
  • 2voh - mBcl-2A1 + Bak BH3 peptide
    
  • 2voi - mBcl-2A1 + BID BH3 peptide
    
  • 3mqp - hBcl-2A1 + Noxa BH3 peptide
    
  • 5uul - hBcl-2A1 + PUMA BH3 peptide
    
  • 5uuk, 5uup - hBcl-2A1 + Bfl-1 peptide
    
  • 4zeq - hBcl-2A1 + BID BH3 peptide
    

• Bcl-3

• • 1k1a, 1k1b – hBcl-3 ankyrin repeat domain
    

• Bcl-6

• • 3e4u, 1r28, 1r29, 4u2m – hBcl-6 BTB domain
    
  • 3lbz, 5mw6, 5mw2, 5mwd, 5n1x, 5n1z, 5n20, 5n21, 5x4m, 5x4n, 5x4o, 5x4p, 5x9o, 5x9p, 5x4o – hBcl-6 BTB domain + inhibitor
    
  • 4cp3 – hBcl-6 BTB domain + antibiotic
    
  • 3bim – hBcl-6 BTB domain (mutant) + Bcl-6 corepressor
    
  • 5h7g, 5h7h – hBcl-6 BTB domain + F1324 peptide
    
  • 1r2b – hBcl-6 BTB domain + SMRT peptide
    
  • 2lce – hBcl-6 zinc fingers 2-3 - NMR
    

• Bcl-9

• • 3sl9 – hBcl-9 residues 344-396 + catenin beta-1
    

• Bcl-10

• • 2mb9 – hBcl-10 CARD domain (mutant) – NMR
    
  • 6bze – hBcl-10 CARD domain – Cryo EM
    

• Bcl-W (Bcl-2-like protein 2)

• • 1o0l, 1mk3, 2y6w – hBcl-W (mutant)
    
  • 1zy3, 4cim - hBcl-W (mutant) + BID BH3 peptide
    
  • 4k5a, 4k5b - Bcl-W (mutant) + ankyrin repeat - bovine
    
  • 4cin - hBcl-W + BH3 peptide
    

• Bcl-2-like protein 4 (Bax)

• • 4bd7, 4s0o, 4s0p - hBax
    
  • 4bd8 – hBax (mutant)
    
  • 2lr1 - hBax + VMIA peptide
    
  • 4bd6 – hBax (mutant) + BH3 peptide
    
  • 2k7w – hBax + BIM BH3 peptide - NMR
    
  • 4zie, 4zif, 4zig, 4zih, 4zii, 5vww – hBax (mutant) + BIM BH3 peptide
    
  • 4bd2 – hBax (mutant) + BID BH3 peptide
    

• Bcl-2-like protein 5

• • 3i1h - hBcl-2-L-5 + hBak
    

• Bcl-2-like protein 7 (Bak, Bcl-2 homologous antagonist/killer)

• • 2yv6, 2imt, 2jcn, 2ims – hBak
    
  • 5fmi, 4u2u, 5vx1 – hBak (mutant)
    
  • 4u2v – hBak/GFP
    
  • 3qbr - hBak + sjA
    
  • 2xpx - hBak fragment + BHRF1
    
  • 5vwx, 5vwy, 5vwz, 5vx0 - hBak + BIM BH3 domain
    
  • 5vwv - hBak (mutant)+ BIM BH3 domain
    
  • 2m5b - hBak + BID BH3 domain - NMR
    

• Bcl-2-like protein 10

• • 2kua – mBcl-2-L-10
    
  • 4b4s - hBcl-2-L-10 + hBIM BH3 peptide
    

• Bcl-2-like protein 11 (BIM)

• • 2nl9 – hBIM + Mcl-1
    

Mcl-1 (Bcl-2-like protein 3)

• • 1wsx – mMcl-1 residues 152-308 - NMR
    
  • 3mk8 - hMcl-1 fragment
    
  • 2mhs - hMcl-1 fragment (mutant)
    
  • 4wms - hMcl-1/MBP (mutant)
    
  • 5lof - hMcl-1/MBP + inhibitor
    
  • 4wmx, 4wmw, 4wmv - hMcl-1/MBP + ligand
    
  • 4wmu, 4wmt - hMcl-1/MBP (mutant) + ligand
    
  • 4wgi - hMcl-1/MBP (mutant) + macrolactam
    

3wix, 3wiy, 4oq5, 4oq6, 4hw2, 4hw3, 4hw4, 4wmr, 4zbf, 4zbi, 5fc4, 5fdo, 5fdr, 5iez, 5if4, 5jsb, 5ku9, 5vkc, 6b4l, 6b4u, 6bw2, 6bw8 - hMcl-1 fragment + inhibitor

• • 5uum - hMcl-1 fragment + FS2 peptide
    
  • 5c3f - hMcl-1 fragment + BIB MM
    
  • 5mes, 5mev - hMcl-1 fragment + inhibitor + antibody
    

• Mcl-1 complex with BH3 domain peptide

• • 2nla, 4g35 – rMcl-1 fragment + NoxaB BH3 domain
    
  • 2jm6, 2rod – mMcl-1 fragment + NoxaB fragment – NMR
    
  • 2roc - mMcl-1 fragment + Puma BH3 domain
    
  • 3kz0 - hMcl-1 + MB7 BH3 domain
    
  • 3pk1 – hMcl-1 fragment + hBax BH3 domain
    
  • 2kbw - hMcl-1 fragment + BID BH3 peptide – NMR
    
  • 4bpj, 4bpi - hMcl-1 fragment + Puma BH3 peptide
    
  • 5c6h - hMcl-1 fragment + Mule BH3 peptide
    
  • 5w89, 5w8f, 3kj0, 3kj1, 3kj2, 3io9, 3d7v, 2pqk, 5vx2 - hMcl-1 fragment + BIM BH3 peptide
    
  • 2kbw - hMcl-1 fragment + BID BH3 peptide - NMR
    

• M11

• • 2o42, 2jbx – MvM11L – Myxoma virus
    
  • 2jby – MvM11L + Bcl-2 homologous antagonist/killer
    
  • 3dvu, 3bl2, 4mi8 – M11 + Beclin-1 – Murid herpesvirus
    

N1L

• • 2i39 – VvN1L – Vaccinia virus
    
  • 4bbb, 4bbc, 4bbd – VvN1L (mutant)
    

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References

1. Mee Young Hong; Chapkin, Robert S.; Davidson, Laurie A.; Turner, Nancy D.; Morris, Jeffrey S.; Carroll, Raymond J.; Lupton, Joanne R.. Nutrition & Cancer, 2003, Vol. 46 Issue 1, p44-44, 8p; DOI: NO_DOI; (AN 10719727)

2. Reed JC, Zha H, Aime-Sempe C, Takayama S, Wang HG, Advances In Experimental Medicine And Biology, ISSN: 0065-2598, 1996; Vol. 406, pp. 99-112; PMID: 8910675