6hyl

From Proteopedia

Jump to: navigation, search

Structure of PCM1 LIR motif bound to GABARAP

Structural highlights

6hyl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.559Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PCM1_HUMAN Differentiated thyroid carcinoma. A chromosomal aberration involving PCM1 is found in papillary thyroid carcinomas (PTCs) (PubMed:10980597). Translocation t(8;10)(p21.3;q11.2) with RET links the protein kinase domain of RET to the major portion of PCM1 (PubMed:10980597).[1] A chromosomal aberration involving PCM1 is found in a variety of hematological malignancies including atypical chronic myeloid leukemia (atypical CML) and T-cell lymphoma (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865). Translocation t(8;9)(p22;p24) with JAK2 links the protein kinase domain of JAK2 to the major portion of PCM1 (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865).[2] [3] [4] [5] [6]

Function

GBRAP_HUMAN May play a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy (By similarity).[7] PCM1_HUMAN Required for centrosome assembly and function (PubMed:12403812, PubMed:15659651, PubMed:16943179). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (PubMed:12403812, PubMed:15659651). Required to anchor microtubules to the centrosome (PubMed:12403812, PubMed:15659651). Involved in the biogenesis of cilia (PubMed:20551181, PubMed:24121310).[8] [9] [10] [11] [12]

Publication Abstract from PubMed

Autophagy is an essential recycling and quality control pathway. Mammalian ATG8 proteins drive autophagosome formation and selective removal of protein aggregates and organelles by recruiting autophagy receptors and adaptors that contain a LC3-interacting region (LIR) motif. LIR motifs can be highly selective for ATG8 subfamily proteins (LC3s/GABARAPs), however the molecular determinants regulating these selective interactions remain elusive. Here we show that residues within the core LIR motif and adjacent C-terminal region as well as ATG8 subfamily-specific residues in the LIR docking site are critical for binding of receptors and adaptors to GABARAPs. Moreover, rendering GABARAP more LC3B-like impairs autophagy receptor degradation. Modulating LIR binding specificity of the centriolar satellite protein PCM1, implicated in autophagy and centrosomal function, alters its dynamics in cells. Our data provides new mechanistic insight into how selective binding of LIR motifs to GABARAPs is achieved, and elucidate the overlapping and distinct functions of ATG8 subfamily proteins.

Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins.,Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6. PMID:31053714[13]

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

Loading citation details..
Citations
13 reviews cite this structure
The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson's Disease.
Lin et al. (2019)
12 more
43 other articles
No citations found

See Also

References

  1. ↑ Corvi R, Berger N, Balczon R, Romeo G. RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma. Oncogene. 2000 Aug 31;19(37):4236-42. PMID:10980597 doi:http://dx.doi.org/10.1038/sj.onc.1203772
  2. ↑ Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC. The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res. 2005 Apr 1;65(7):2662-7. PMID:15805263 doi:http://dx.doi.org/65/7/2662
  3. ↑ Murati A, Gelsi-Boyer V, Adelaide J, Perot C, Talmant P, Giraudier S, Lode L, Letessier A, Delaval B, Brunel V, Imbert M, Garand R, Xerri L, Birnbaum D, Mozziconacci MJ, Chaffanet M. PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia. 2005 Sep;19(9):1692-6. doi: 10.1038/sj.leu.2403879. PMID:16034466 doi:http://dx.doi.org/10.1038/sj.leu.2403879
  4. ↑ Bousquet M, Quelen C, De Mas V, Duchayne E, Roquefeuil B, Delsol G, Laurent G, Dastugue N, Brousset P. The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene. 2005 Nov 3;24(48):7248-52. PMID:16091753 doi:http://dx.doi.org/1208850
  5. ↑ Adelaide J, Perot C, Gelsi-Boyer V, Pautas C, Murati A, Copie-Bergman C, Imbert M, Chaffanet M, Birnbaum D, Mozziconacci MJ. A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. Leukemia. 2006 Mar;20(3):536-7. doi: 10.1038/sj.leu.2404104. PMID:16424865 doi:http://dx.doi.org/10.1038/sj.leu.2404104
  6. ↑ Bacher U, Reiter A, Haferlach T, Mueller L, Schnittger S, Kern W, Schoch C. A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia. Haematologica. 2006 Jun;91(6):817-20. PMID:16769584
  7. ↑ Lee JH, Rho SB, Chun T. GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnol Lett. 2005 May;27(9):623-8. PMID:15977068 doi:http://dx.doi.org/10.1007/s10529-005-3628-2
  8. ↑ Dammermann A, Merdes A. Assembly of centrosomal proteins and microtubule organization depends on PCM-1. J Cell Biol. 2002 Oct 28;159(2):255-66. doi: 10.1083/jcb.200204023. Epub 2002 Oct, 28. PMID:12403812 doi:http://dx.doi.org/10.1083/jcb.200204023
  9. ↑ Hames RS, Crookes RE, Straatman KR, Merdes A, Hayes MJ, Faragher AJ, Fry AM. Dynamic recruitment of Nek2 kinase to the centrosome involves microtubules, PCM-1, and localized proteasomal degradation. Mol Biol Cell. 2005 Apr;16(4):1711-24. doi: 10.1091/mbc.e04-08-0688. Epub 2005, Jan 19. PMID:15659651 doi:http://dx.doi.org/10.1091/mbc.e04-08-0688
  10. ↑ Srsen V, Gnadt N, Dammermann A, Merdes A. Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle. J Cell Biol. 2006 Aug 28;174(5):625-30. doi: 10.1083/jcb.200606051. PMID:16943179 doi:http://dx.doi.org/10.1083/jcb.200606051
  11. ↑ Sedjai F, Acquaviva C, Chevrier V, Chauvin JP, Coppin E, Aouane A, Coulier F, Tolun A, Pierres M, Birnbaum D, Rosnet O. Control of ciliogenesis by FOR20, a novel centrosome and pericentriolar satellite protein. J Cell Sci. 2010 Jul 15;123(Pt 14):2391-401. doi: 10.1242/jcs.065045. Epub 2010, Jun 15. PMID:20551181 doi:http://dx.doi.org/10.1242/jcs.065045
  12. ↑ Villumsen BH, Danielsen JR, Povlsen L, Sylvestersen KB, Merdes A, Beli P, Yang YG, Choudhary C, Nielsen ML, Mailand N, Bekker-Jensen S. A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis. EMBO J. 2013 Nov 27;32(23):3029-40. doi: 10.1038/emboj.2013.223. Epub 2013 Oct, 11. PMID:24121310 doi:http://dx.doi.org/10.1038/emboj.2013.223
  13. ↑ Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6. PMID:31053714 doi:http://dx.doi.org/10.1038/s41467-019-10059-6

Contents


PDB ID 6hyl

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6hyl"
Personal tools