5lnc

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Structure of SPX domain of the yeast inorganic polyphophate polymerase Vtc4 crystallized by carrier-driven crystallization in fusion with the macro domain of human histone macroH2A1.1

Structural highlights

5lnc is a 2 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.29Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

H2AY_HUMAN Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Involved in stable X chromosome inactivation. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.[1] [2] [3] [4] [5] VTC4_YEAST Component of the vacuolar transporter chaperone (VTC) complex, which plays a role in vacuolar membrane fusion. Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation.[6] [7] [8]

Publication Abstract from PubMed

Obtaining well-ordered crystals remains a significant challenge in protein X-ray crystallography. Carrier-driven crystallization can facilitate crystal formation and structure solution of difficult target proteins. We obtained crystals of the small and highly flexible SPX domain from the yeast vacuolar transporter chaperone 4 (Vtc4) when fused to a C-terminal, non-cleavable macro tag derived from human histone macroH2A1.1. Initial crystals diffracted to 3.3 A resolution. Reductive protein methylation of the fusion protein yielded a new crystal form diffracting to 2.1 A. The structures were solved by molecular replacement, using isolated macro domain structures as search models. Our findings suggest that macro domain tags can be employed in recombinant protein expression in E. coli, and in carrier-driven crystallization.

The macro domain as fusion tag for carrier-driven crystallization.,Wild R, Hothorn M Protein Sci. 2016 Oct 24. doi: 10.1002/pro.3073. PMID:27774698[9]

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

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Citations
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Viral macrodomains: a structural and evolutionary assessment of the pharmacological potential.
Rack et al. (2020)
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References

  1. ↑ Angelov D, Molla A, Perche PY, Hans F, Cote J, Khochbin S, Bouvet P, Dimitrov S. The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell. 2003 Apr;11(4):1033-41. PMID:12718888
  2. ↑ Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell. 2005 Jan;8(1):19-30. PMID:15621527 doi:S1534580704004083
  3. ↑ Hernandez-Munoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40. Epub 2005 May 16. PMID:15897469 doi:0408918102
  4. ↑ Doyen CM, An W, Angelov D, Bondarenko V, Mietton F, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S. Mechanism of polymerase II transcription repression by the histone variant macroH2A. Mol Cell Biol. 2006 Feb;26(3):1156-64. PMID:16428466 doi:10.1128/MCB.26.3.1156-1164.2006
  5. ↑ Chakravarthy S, Gundimella SK, Caron C, Perche PY, Pehrson JR, Khochbin S, Luger K. Structural characterization of the histone variant macroH2A. Mol Cell Biol. 2005 Sep;25(17):7616-24. PMID:16107708 doi:http://dx.doi.org/25/17/7616
  6. ↑ Ogawa N, DeRisi J, Brown PO. New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Mol Biol Cell. 2000 Dec;11(12):4309-21. PMID:11102525
  7. ↑ Muller O, Bayer MJ, Peters C, Andersen JS, Mann M, Mayer A. The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex formation. EMBO J. 2002 Feb 1;21(3):259-69. PMID:11823419 doi:http://dx.doi.org/10.1093/emboj/21.3.259
  8. ↑ Muller O, Neumann H, Bayer MJ, Mayer A. Role of the Vtc proteins in V-ATPase stability and membrane trafficking. J Cell Sci. 2003 Mar 15;116(Pt 6):1107-15. PMID:12584253
  9. ↑ Wild R, Hothorn M. The macro domain as fusion tag for carrier-driven crystallization. Protein Sci. 2016 Oct 24. doi: 10.1002/pro.3073. PMID:27774698 doi:http://dx.doi.org/10.1002/pro.3073

Contents


PDB ID 5lnc

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