7lt6

Structure of Partial Beta-Hairpin LIR from FNIP2 Bound to GABARAPStructure of Partial Beta-Hairpin LIR from FNIP2 Bound to GABARAP

Structural highlights

7lt6 is a 3 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 1.8Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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).^[1] FNIP2_HUMAN Acts as a co-chaperone of HSP90AA1. Inhibits the ATPase activity of HSP90AA1 leading to reduction in its chaperone activity. Facilitates the binding of client protein FLCN to HSP90AA1 (PubMed:27353360). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity). May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways (PubMed:18403135). May regulate phosphorylation of RPS6KB1 (PubMed:18663353).[UniProtKB:Q80TD3]^[2] ^[3] ^[4]

Publication Abstract from PubMed

[Figure: see text].

GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis.,Goodwin JM, Walkup WG 4th, Hooper K, Li T, Kishi-Itakura C, Ng A, Lehmberg T, Jha A, Kommineni S, Fletcher K, Garcia-Fortanet J, Fan Y, Tang Q, Wei M, Agrawal A, Budhe SR, Rouduri SR, Baird D, Saunders J, Kiselar J, Chance MR, Ballabio A, Appleton BA, Brumell JH, Florey O, Murphy LO Sci Adv. 2021 Oct;7(40):eabj2485. doi: 10.1126/sciadv.abj2485. Epub 2021 Oct 1. PMID:34597140^[5]

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

References

↑ 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
↑ Hasumi H, Baba M, Hong SB, Hasumi Y, Huang Y, Yao M, Valera VA, Linehan WM, Schmidt LS. Identification and characterization of a novel folliculin-interacting protein FNIP2. Gene. 2008 May 31;415(1-2):60-7. doi: 10.1016/j.gene.2008.02.022. Epub 2008 Mar, 4. PMID:18403135 doi:http://dx.doi.org/10.1016/j.gene.2008.02.022
↑ Takagi Y, Kobayashi T, Shiono M, Wang L, Piao X, Sun G, Zhang D, Abe M, Hagiwara Y, Takahashi K, Hino O. Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. Oncogene. 2008 Sep 11;27(40):5339-47. doi: 10.1038/onc.2008.261. Epub 2008 Jul, 28. PMID:18663353 doi:http://dx.doi.org/10.1038/onc.2008.261
↑ Woodford MR, Dunn DM, Blanden AR, Capriotti D, Loiselle D, Prodromou C, Panaretou B, Hughes PF, Smith A, Ackerman W, Haystead TA, Loh SN, Bourboulia D, Schmidt LS, Marston Linehan W, Bratslavsky G, Mollapour M. The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat Commun. 2016 Jun 29;7:12037. doi: 10.1038/ncomms12037. PMID:27353360 doi:http://dx.doi.org/10.1038/ncomms12037
↑ Goodwin JM, Walkup WG 4th, Hooper K, Li T, Kishi-Itakura C, Ng A, Lehmberg T, Jha A, Kommineni S, Fletcher K, Garcia-Fortanet J, Fan Y, Tang Q, Wei M, Agrawal A, Budhe SR, Rouduri SR, Baird D, Saunders J, Kiselar J, Chance MR, Ballabio A, Appleton BA, Brumell JH, Florey O, Murphy LO. GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis. Sci Adv. 2021 Oct;7(40):eabj2485. PMID:34597140 doi:10.1126/sciadv.abj2485

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OCA

[1] 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

[2] Hasumi H, Baba M, Hong SB, Hasumi Y, Huang Y, Yao M, Valera VA, Linehan WM, Schmidt LS. Identification and characterization of a novel folliculin-interacting protein FNIP2. Gene. 2008 May 31;415(1-2):60-7. doi: 10.1016/j.gene.2008.02.022. Epub 2008 Mar, 4. PMID:18403135 doi:http://dx.doi.org/10.1016/j.gene.2008.02.022

[3] Takagi Y, Kobayashi T, Shiono M, Wang L, Piao X, Sun G, Zhang D, Abe M, Hagiwara Y, Takahashi K, Hino O. Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. Oncogene. 2008 Sep 11;27(40):5339-47. doi: 10.1038/onc.2008.261. Epub 2008 Jul, 28. PMID:18663353 doi:http://dx.doi.org/10.1038/onc.2008.261

[4] Woodford MR, Dunn DM, Blanden AR, Capriotti D, Loiselle D, Prodromou C, Panaretou B, Hughes PF, Smith A, Ackerman W, Haystead TA, Loh SN, Bourboulia D, Schmidt LS, Marston Linehan W, Bratslavsky G, Mollapour M. The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat Commun. 2016 Jun 29;7:12037. doi: 10.1038/ncomms12037. PMID:27353360 doi:http://dx.doi.org/10.1038/ncomms12037

[5] Goodwin JM, Walkup WG 4th, Hooper K, Li T, Kishi-Itakura C, Ng A, Lehmberg T, Jha A, Kommineni S, Fletcher K, Garcia-Fortanet J, Fan Y, Tang Q, Wei M, Agrawal A, Budhe SR, Rouduri SR, Baird D, Saunders J, Kiselar J, Chance MR, Ballabio A, Appleton BA, Brumell JH, Florey O, Murphy LO. GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis. Sci Adv. 2021 Oct;7(40):eabj2485. PMID:34597140 doi:10.1126/sciadv.abj2485

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