7ea2

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crystal structure of NAP1 FIR in complex with RB1CC1 Claw domain

Structural highlights

7ea2 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 2.14Å
Ligands:FLC, P6G, PEG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RBCC1_HUMAN Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity).[UniProtKB:Q9ESK9][1] [2] [3] [4] [5] [6] [7] AZI2_HUMAN Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity. Activates serine/threonine-protein kinase TBK1 and facilitates its oligomerization. Enhances the phosphorylation of NF-kappa-B p65 subunit RELA by TBK1. Promotes TBK1-induced as well as TNF-alpha or PMA-induced activation of NF-kappa-B. Participates in IFNB promoter activation via TICAM1.[8] [9] [10]

Publication Abstract from PubMed

The recruitment of Unc-51-like kinase and TANK-binding kinase 1 complexes is essential for Nuclear dot protein 52-mediated selective autophagy and relies on the specific association of NDP52, RB1-inducible coiled-coil protein 1, and Nak-associated protein 1 (5-azacytidine-induced protein 2, AZI2). However, the underlying molecular mechanism remains elusive. Here, we find that except for the NDP52 SKIP carboxyl homology (SKICH)/RB1CC1 coiled-coil interaction, the LC3-interacting region of NDP52 can directly interact with the RB1CC1 Claw domain, as that of NAP1 FIP200-binding region (FIR). The determined crystal structures of NDP52 SKICH/RB1CC1 complex, NAP1 FIR/RB1CC1 complex, and the related NAP1 FIR/Gamma-aminobutyric acid receptor-associated protein complex not only elucidate the molecular bases underpinning the interactions of RB1CC1 with NDP52 and NAP1 but also reveal that RB1CC1 Claw and Autophagy-related protein 8 family proteins are competitive in binding to NAP1 and NDP52. Overall, our findings provide mechanistic insights into the interactions of NDP52, NAP1 with RB1CC1 and ATG8 family proteins.

Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52.,Fu T, Zhang M, Zhou Z, Wu P, Peng C, Wang Y, Gong X, Li Y, Wang Y, Xu X, Li M, Shen L, Pan L Sci Adv. 2021 Aug 13;7(33). pii: 7/33/eabi6582. doi: 10.1126/sciadv.abi6582., Print 2021 Aug. PMID:34389544[11]

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

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Citations
2 reviews cite this structure
The mechanisms and roles of selective autophagy in mammals.
Vargas et al. (2023)
1 more
3 other articles
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References

  1. ↑ Ueda H, Abbi S, Zheng C, Guan JL. Suppression of Pyk2 kinase and cellular activities by FIP200. J Cell Biol. 2000 Apr 17;149(2):423-30. PMID:10769033
  2. ↑ Chano T, Ikegawa S, Saito-Ohara F, Inazawa J, Mabuchi A, Saeki Y, Okabe H. Isolation, characterization and mapping of the mouse and human RB1CC1 genes. Gene. 2002 May 29;291(1-2):29-34. PMID:12095676
  3. ↑ Chano T, Saeki Y, Serra M, Matsumoto K, Okabe H. Preferential expression of RB1-inducible coiled-coil 1 in terminal differentiated musculoskeletal cells. Am J Pathol. 2002 Aug;161(2):359-64. doi: 10.1016/S0002-9440(10)64190-9. PMID:12163359 doi:http://dx.doi.org/10.1016/S0002-9440(10)64190-9
  4. ↑ Abbi S, Ueda H, Zheng C, Cooper LA, Zhao J, Christopher R, Guan JL. Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Mol Biol Cell. 2002 Sep;13(9):3178-91. doi: 10.1091/mbc.e02-05-0295. PMID:12221124 doi:http://dx.doi.org/10.1091/mbc.e02-05-0295
  5. ↑ Kontani K, Chano T, Ozaki Y, Tezuka N, Sawai S, Fujino S, Saeki Y, Okabe H. RB1CC1 suppresses cell cycle progression through RB1 expression in human neoplastic cells. Int J Mol Med. 2003 Nov;12(5):767-9. PMID:14533007
  6. ↑ Morselli E, Shen S, Ruckenstuhl C, Bauer MA, Marino G, Galluzzi L, Criollo A, Michaud M, Maiuri MC, Chano T, Madeo F, Kroemer G. p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200. Cell Cycle. 2011 Aug 15;10(16):2763-9. doi: 10.4161/cc.10.16.16868. Epub 2011 Aug, 15. PMID:21775823 doi:http://dx.doi.org/10.4161/cc.10.16.16868
  7. ↑ Nishimura T, Kaizuka T, Cadwell K, Sahani MH, Saitoh T, Akira S, Virgin HW, Mizushima N. FIP200 regulates targeting of Atg16L1 to the isolation membrane. EMBO Rep. 2013 Mar 1;14(3):284-91. doi: 10.1038/embor.2013.6. Epub 2013 Feb 8. PMID:23392225 doi:http://dx.doi.org/10.1038/embor.2013.6
  8. ↑ Fujita F, Taniguchi Y, Kato T, Narita Y, Furuya A, Ogawa T, Sakurai H, Joh T, Itoh M, Delhase M, Karin M, Nakanishi M. Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. Mol Cell Biol. 2003 Nov;23(21):7780-93. PMID:14560022
  9. ↑ Sasai M, Oshiumi H, Matsumoto M, Inoue N, Fujita F, Nakanishi M, Seya T. Cutting Edge: NF-kappaB-activating kinase-associated protein 1 participates in TLR3/Toll-IL-1 homology domain-containing adapter molecule-1-mediated IFN regulatory factor 3 activation. J Immunol. 2005 Jan 1;174(1):27-30. PMID:15611223
  10. ↑ Goncalves A, Burckstummer T, Dixit E, Scheicher R, Gorna MW, Karayel E, Sugar C, Stukalov A, Berg T, Kralovics R, Planyavsky M, Bennett KL, Colinge J, Superti-Furga G. Functional dissection of the TBK1 molecular network. PLoS One. 2011;6(9):e23971. doi: 10.1371/journal.pone.0023971. Epub 2011 Sep 8. PMID:21931631 doi:http://dx.doi.org/10.1371/journal.pone.0023971
  11. ↑ Fu T, Zhang M, Zhou Z, Wu P, Peng C, Wang Y, Gong X, Li Y, Wang Y, Xu X, Li M, Shen L, Pan L. Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52. Sci Adv. 2021 Aug 13;7(33):eabi6582. PMID:34389544 doi:10.1126/sciadv.abi6582

Contents


PDB ID 7ea2

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