FK506 binding protein
From Proteopedia
FunctionFK506 binding protein (FKBP) is a prolyl isomerase related to the cyclophilins. FKBP is a folding chaperone for proteins containing prolines[1].
For more details see
RelevanceFKBP12 binds the immunosuppressor tacrolimus (ascomycin FK506) which is used against organ rejection and rapamycin[18]. DiseaseMutations in FKBP14 cause Ehlers-Danlos syndrome[19].
Wheat FKBP73 and its comparison with human FKBP52[20]Ribbon representation of the three FKBP domains; wFK73_1 (residues 1–148) in blueviolet, wFK73_2 (residues 149–266) in cyan and wFK73_3 (residues 267–386) in magenta (3jym). The wFK73_1 domain exhibits electron density only between residues 33–38, 54–69 and 87–148. The bulges and the flaps as well as the N- and C-termini are labeled. The three FK506 binding (FK) domains of wFKBP73 are held together mainly by salt bridge networks situated between each pair of domains. The wFK73_2-wFK73_1 domains are held by a salt bridge between Lys162–Glu62, and a salt bridge network between Arg151–Asp61 and Glu58. The interface between wFK73_2-wFK73_3 is held by two salt bridges between Lys204–Glu269, and Glu178–Lys279. The interactions Lys162–Glu62 and Glu178–Lys279, involve conserved residues (Glu62 from wFK73_1 and Glu178 from wFK73_2, Lys162 from wFK73_2 and Lys279 from wFK73_3). The 3D structures of several FKBP family members from various species are solved, most of them comprise 1-2 FK domains (e.g. human FKBP52, known also as FKBP4), while wFKBP73 has 3 FK domains which is characteristic to plants. A sequence-based structure comparison between each of the 3 FK domains of wFKBP73 and the 2 FK domains of hFKBP52 (1q1c) was performed. All 3 FK domains of wFKBP73 adopt a typical FK fold exhibiting significant diversity when superimposed. They are arranged in a linear manner in space as observed in the 2 FK domains of hFKBP52. While the 2 FK domains of hFKBP52 are in the same orientation, the orientation between any 2 consecutive wFK73 domains is different than that between the two FK domains of hFKBP52. Superposition of the wFK73_1 (in blueviolet) and wFK73_2 (in cyan) domains on hFK52_1 (in yellow) and hFK52_2 (in blue) revealed that while wFK73_2 is perfectly aligned with hFK52_2, N-terminal wFK73_1 does not align with hFK52_1 (yellow). Similarly, superposition of the wFK73_2 and wFK73_3 (in magenta) domains on hFKBP52 revealed that while wFK73_2 is perfectly aligned with hFK52_1 (in yellow), wFK73_3 does not align with hFK52_2. This unique arrangement of wFKBP73 causes that the α-helices of wFKBP73 3 FK domains are exposed on the same surface, while the 2 α-helices of hFK52 are presented on opposite surfaces. It was shown that 12 conserved residues (for wFK73_1 domain they are Tyr67, Phe77, Asp78, Arg83, Phe87, Gln95, Val96, Ile97, Trp100, Tyr123, Ile132, and Phe140) of the FK1 domains of hFKBP12, 13, 25, 51 and 52, are involved in binding the FK506 or rapamycin. Since only the FK1 domains contain all the conserved amino acids (in contrast to FK2 and/or FK3 domains), only they exhibit PPIase activity, which can be inhibited by the binding of the drugs FK506, and rapamycin. These conserved residues form the hydrophobic cavity. The structure of hFKBP12 (2ppn) demonstrates a good example of this cavity. All these residues are conserved in the wFK73_1 domain, it could be assumed that a similar cavity is also formed in wFK73_1, although some of these residues are missing electron density in the wFK73 structure and, therefore, it can not be seen. Domain wFK73_3 has narrower cavity, whereas wFK73_2 lacks this cavity at all. Conserved residues are colored yellow. So, the lack of drug binding of the wFK73_2 and wFK73_3 domains could be explained by the absence of the conserved drug binding residues. This is in agreement with the fact that the FK2 domains of hFKBP51 and hFKBP52 and the single FK domains of FKBP38, DmFKBP45 and AtFKBP42, all lacking the conserved residues, do not exhibit drug binding. SlyD[21]SlyD belongs to the FK506-binding protein (FKBP) family with both peptidylprolyl isomerase (PPIase) and chaperone activities, and is considered to be a ubiquitous cytosolic protein-folding facilitator in bacteria. It possesses a histidine- and cysteine-rich C-terminus binding to selected divalent metal ions (e.g., Ni2+, Zn2+), which is important for its involvement in the maturation processes of metalloenzymes. The solution structure of C-terminus-truncated SlyD from Helicobacter pylori (HpSlyDΔC) was determined (2kr7). HpSlyDΔC folds into two well-separated, orientation-independent domains: the PPIase-active FKBP domain (in cyan) and the chaperone-active insert-in-flap (IF) domain (in red), linkers are in darkmagenta. The FKBP domain consists of a four-stranded antiparallel β-sheet with an α-helix on one side, whereas the IF domain folds into a four-stranded antiparallel β-sheet accompanied by a short α-helix. Intact H. pylori SlyD binds both Ni2+ and Zn2+, with dissociation constants of 2.74 and 3.79 μM respectively. Intriguingly, binding of Ni2+ instead of Zn2+ induces protein conformational changes around the active sites of the FKBP domain, implicating a regulatory role of nickel (residues experiencing relatively large chemical shift perturbations upon interactions of HpSlyDΔC with Ni2+ are in blueviolet). The twin-arginine translocation (Tat) signal peptide from the small subunit of [NiFe] hydrogenase (HydA) binds the protein at the IF domain (residues in orange). Surprisingly, several residues (Ile41, Gly42, Ile46, and Asn31) were from the FKBP domain, which is likely due to the binding of the longer n-region of HydA Tat peptide to the FKBP domain. Nickel binding and the recognition of the Tat signal peptide by the protein suggest that SlyD participates in [NiFe] hydrogenase maturation processes. 3D Structures of FKBP |
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References
- ↑ Kang CB, Hong Y, Dhe-Paganon S, Yoon HS. FKBP family proteins: immunophilins with versatile biological functions. Neurosignals. 2008;16(4):318-25. doi: 10.1159/000123041. Epub 2008 Jul 18. PMID:18635947 doi:http://dx.doi.org/10.1159/000123041
- ↑ Yang X, Zhao X, Zhu Y, Shen Y, Wang Y, Lu P, Jiang Z, Pan H, Yang J, Xun J, Zhao L, Wang J, Liang Z, Shen X, Liang Y, Lin Q, Liang H, Jin L, Zhang D, Liu J, Wang B, Jiang S, Xu J, Wu H, Lu H, Zhu H. FKBP3 Induces Human Immunodeficiency Virus Type 1 Latency by Recruiting Histone Deacetylase 1/2 to the Viral Long Terminal Repeat. mBio. 2021 Aug 31;12(4):e0079521. PMID:34281390 doi:10.1128/mBio.00795-21
- ↑ Misaka T, Murakawa T, Nishida K, Omori Y, Taneike M, Omiya S, Molenaar C, Uno Y, Yamaguchi O, Takeda J, Shah AM, Otsu K. FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice. J Mol Cell Cardiol. 2018 Jan;114:93-104. PMID:29129702 doi:10.1016/j.yjmcc.2017.11.004
- ↑ Aghdasi B, Ye K, Resnick A, Huang A, Ha HC, Guo X, Dawson TM, Dawson VL, Snyder SH. FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2425-30. PMID:11226255 doi:10.1073/pnas.041614198
- ↑ Wehrens XH, Lehnart SE, Huang F, Vest JA, Reiken SR, Mohler PJ, Sun J, Guatimosim S, Song LS, Rosemblit N, D'Armiento JM, Napolitano C, Memmi M, Priori SG, Lederer WJ, Marks AR. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell. 2003 Jun 27;113(7):829-40. PMID:12837242 doi:10.1016/s0092-8674(03)00434-3
- ↑ Tat V, Ayaub EA, Ayoub A, Vierhout M, Naiel S, Padwal MK, Abed S, Mekhael O, Tandon K, Revill SD, Yousof T, Bellaye PS, Kolb PS, Dvorkin-Gheva A, Naqvi A, Cutz JC, Hambly N, Kato J, Vaughan M, Moss J, Kolb MRJ, Ask K. FK506-Binding Protein 13 Expression Is Upregulated in Interstitial Lung Disease and Correlated with Clinical Severity. A Potentially Protective Role. Am J Respir Cell Mol Biol. 2021 Feb;64(2):235-246. PMID:33253593 doi:10.1165/rcmb.2020-0121OC
- ↑ Budiman C, Bando K, Angkawidjaja C, Koga Y, Takano K, Kanaya S. Engineering of monomeric FK506-binding protein 22 with peptidyl prolyl cis-trans isomerase. Importance of a V-shaped dimeric structure for binding to protein substrate. FEBS J. 2009 Aug;276(15):4091-101. PMID:19558490 doi:10.1111/j.1742-4658.2009.07116.x
- ↑ Dilworth D, Gong F, Miller K, Nelson CJ. FKBP25 participates in DNA double-strand break repair. Biochem Cell Biol. 2020 Feb;98(1):42-49. PMID:30620620 doi:10.1139/bcb-2018-0328
- ↑ Atack TC, Raymond DD, Blomquist CA, Pasaje CF, McCarren PR, Moroco J, Befekadu HB, Robinson FP, Pal D, Esherick LY, Ianari A, Niles JC, Sellers WR. Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35. ACS Med Chem Lett. 2020 Sep 1;11(11):2131-2138. PMID:33209191 doi:10.1021/acsmedchemlett.0c00272
- ↑ Jarczowski F, Jahreis G, Erdmann F, Schierhorn A, Fischer G, Edlich F. FKBP36 is an inherent multifunctional glyceraldehyde-3-phosphate dehydrogenase inhibitor. J Biol Chem. 2009 Jan 9;284(2):766-73. PMID:19001379 doi:10.1074/jbc.M709779200
- ↑ Shirane-Kitsuji M, Nakayama KI. Mitochondria: FKBP38 and mitochondrial degradation. Int J Biochem Cell Biol. 2014 Jun;51:19-22. PMID:24657651 doi:10.1016/j.biocel.2014.03.007
- ↑ Orłowski M, Popławska K, Pieprzyk J, Szczygieł-Sommer A, Więch A, Zarębski M, Tarczewska A, Dobrucki J, Ożyhar A. Molecular determinants of Drosophila immunophilin FKBP39 nuclear localization. Biol Chem. 2018 Apr 25;399(5):467-484. PMID:29337690 doi:10.1515/hsz-2017-0251
- ↑ Granzin J, Eckhoff A, Weiergraber OH. Crystal structure of a multi-domain immunophilin from Arabidopsis thaliana: a paradigm for regulation of plant ABC transporters. J Mol Biol. 2006 Dec 8;364(4):799-809. Epub 2006 Sep 26. PMID:17045295 doi:10.1016/j.jmb.2006.09.052
- ↑ Smedlund KB, Sanchez ER, Hinds TD Jr. FKBP51 and the molecular chaperoning of metabolism. Trends Endocrinol Metab. 2021 Nov;32(11):862-874. PMID:34481731 doi:10.1016/j.tem.2021.08.003
- ↑ Davies TH, Sánchez ER. FKBP52. Int J Biochem Cell Biol. 2005 Jan;37(1):42-7. PMID:15381148 doi:10.1016/j.biocel.2004.03.013
- ↑ Tai PK, Chang H, Albers MW, Schreiber SL, Toft DO, Faber LE. P59 (FK506 binding protein 59) interaction with heat shock proteins is highly conserved and may involve proteins other than steroid receptors. Biochemistry. 1993 Aug 31;32(34):8842-7. PMID:7689858 doi:10.1021/bi00085a015
- ↑ Kurek I, Pirkl F, Fischer E, Buchner J, Breiman A. Wheat FKBP73 functions in vitro as a molecular chaperone independently of its peptidyl prolyl cis-trans isomerase activity. Planta. 2002 May;215(1):119-26. PMID:12012248 doi:10.1007/s00425-001-0722-0
- ↑ Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E, et al.. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation. 1997 Aug 15;64(3):436-43. PMID:9275110
- ↑ Baumann M, Giunta C, Krabichler B, Rüschendorf F, Zoppi N, Colombi M, Bittner RE, Quijano-Roy S, Muntoni F, Cirak S, Schreiber G, Zou Y, Hu Y, Romero NB, Carlier RY, Amberger A, Deutschmann A, Straub V, Rohrbach M, Steinmann B, Rostásy K, Karall D, Bönnemann CG, Zschocke J, Fauth C. Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss. Am J Hum Genet. 2012 Feb 10;90(2):201-16. PMID:22265013 doi:10.1016/j.ajhg.2011.12.004
- ↑ Unger T, Dym O, Albeck S, Jacobovitch Y, Bernehim R, Marom D, Pisanty O, Breiman A. Crystal structure of the three FK506 binding protein domains of wheat FKBP73: evidence for a unique wFK73_2 domain. J Struct Funct Genomics. 2010 Jun;11(2):113-23. Epub 2010 Mar 20. PMID:20306145 doi:10.1007/s10969-010-9085-8
- ↑ Cheng T, Li H, Xia W, Sun H. Multifaceted SlyD from Helicobacter pylori: implication in [NiFe] hydrogenase maturation. J Biol Inorg Chem. 2011 Nov 2. PMID:22045417 doi:10.1007/s00775-011-0855-y