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| | ==Crystal structure of PLEKHM1 LIR in complex with human LC3C_8-125== | | ==Crystal structure of PLEKHM1 LIR in complex with human LC3C_8-125== |
| - | <StructureSection load='5dpw' size='340' side='right' caption='[[5dpw]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='5dpw' size='340' side='right'caption='[[5dpw]], [[Resolution|resolution]] 2.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dpw]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DPW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DPW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dpw]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DPW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dpr|5dpr]], [[5dps|5dps]], [[5dpt|5dpt]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.185Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP1LC3C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PLEKHM1, KIAA0356 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dpw OCA], [https://pdbe.org/5dpw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dpw RCSB], [https://www.ebi.ac.uk/pdbsum/5dpw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dpw ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dpw OCA], [http://pdbe.org/5dpw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dpw RCSB], [http://www.ebi.ac.uk/pdbsum/5dpw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dpw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/PKHM1_HUMAN PKHM1_HUMAN]] Intermediate osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MLP3C_HUMAN MLP3C_HUMAN]] Ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2. Recruites all ATG8 family members to infecting bacteria such as S.Typhimurium.<ref>PMID:23022382</ref> [[http://www.uniprot.org/uniprot/PKHM1_HUMAN PKHM1_HUMAN]] Proposed to act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Seems to be involved in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Involved in vesicular transport in the osteoclast (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7 (PubMed:25500191).[UniProtKB:Q5PQS0]<ref>PMID:12820725</ref> <ref>PMID:20943950</ref> <ref>PMID:25498145</ref> <ref>PMID:25500191</ref> | + | [https://www.uniprot.org/uniprot/MLP3C_HUMAN MLP3C_HUMAN] Ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2. Recruites all ATG8 family members to infecting bacteria such as S.Typhimurium.<ref>PMID:23022382</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Microtubule-associated protein|Microtubule-associated protein]] | + | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Dobson, R C.J]] | + | [[Category: Large Structures]] |
| - | [[Category: Ravichandran, A C]] | + | [[Category: Dobson RCJ]] |
| - | [[Category: Suzuki, H]] | + | [[Category: Ravichandran AC]] |
| - | [[Category: Autophagy]] | + | [[Category: Suzuki H]] |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
MLP3C_HUMAN Ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2. Recruites all ATG8 family members to infecting bacteria such as S.Typhimurium.[1]
Publication Abstract from PubMed
Through the canonical LC3 interaction motif (LIR), [W/F/Y]-X1-X2-[I/L/V], protein complexes are recruited to autophagosomes to perform their functions as either autophagy adaptors or receptors. How these adaptors/receptors selectively interact with either LC3 or GABARAP families remains unclear. Herein, we determine the range of selectivity of 30 known core LIR motifs towards individual LC3s and GABARAPs. From these, we define a G ABARAP I nteraction M otif (GIM) sequence ([W/F]-[V/I]-X2-V) that the adaptor protein PLEKHM1 tightly conforms to. Using biophysical and structural approaches, we show that the PLEKHM1-LIR is indeed 11-fold more specific for GABARAP than LC3B. Selective mutation of the X1 and X2 positions either completely abolished the interaction with all LC3 and GABARAPs or increased PLEKHM1-GIM selectivity 20-fold towards LC3B. Finally, we show that conversion of p62/SQSTM1, FUNDC1 and FIP200 LIRs into our newly defined GIM, by introducing two valine residues, enhances their interaction with endogenous GABARAP over LC3B. The identification of a GABARAP-specific interaction motif will aid the identification and characterization of the expanding array of autophagy receptor and adaptor proteins and their in vivo functions.
Structural and functional analysis of the GABARAP interaction motif (GIM).,Rogov VV, Stolz A, Ravichandran AC, Rios-Szwed DO, Suzuki H, Kniss A, Lohr F, Wakatsuki S, Dotsch V, Dikic I, Dobson RC, McEwan DG EMBO Rep. 2017 Aug;18(8):1382-1396. doi: 10.15252/embr.201643587. Epub 2017 Jun, 27. PMID:28655748[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ von Muhlinen N, Akutsu M, Ravenhill BJ, Foeglein A, Bloor S, Rutherford TJ, Freund SM, Komander D, Randow F. LC3C, bound selectively by a noncanonical LIR motif in NDP52, is required for antibacterial autophagy. Mol Cell. 2012 Nov 9;48(3):329-42. doi: 10.1016/j.molcel.2012.08.024. Epub 2012, Sep 27. PMID:23022382 doi:http://dx.doi.org/10.1016/j.molcel.2012.08.024
- ↑ Rogov VV, Stolz A, Ravichandran AC, Rios-Szwed DO, Suzuki H, Kniss A, Lohr F, Wakatsuki S, Dotsch V, Dikic I, Dobson RC, McEwan DG. Structural and functional analysis of the GABARAP interaction motif (GIM). EMBO Rep. 2017 Aug;18(8):1382-1396. doi: 10.15252/embr.201643587. Epub 2017 Jun, 27. PMID:28655748 doi:http://dx.doi.org/10.15252/embr.201643587
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