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3rbq

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Revision as of 05:56, 15 June 2022

Co-crystal structure of human UNC119 (retina gene 4) and an N-terminal Transducin-alpha mimicking peptide

Structural highlights

3rbq is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	3gqq
Gene:	UNC119, RG4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[U119A_HUMAN] Idiopathic CD4 lymphocytopenia;Cone rod dystrophy. Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. [GNAT1_HUMAN] Congenital stationary night blindness. The disease is caused by mutations affecting the gene represented in this entry.

Function

[U119A_HUMAN] Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells.^[1] ^[2] [GNAT1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.

Publication Abstract from PubMed

UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin alpha (Talpha) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13. The crystal structure of human UNC119 at 1.95-A resolution revealed an immunoglobulin-like beta-sandwich fold. Pulldowns and isothermal titration calorimetry revealed a tight interaction between UNC119 and acylated Galpha peptides. The structure of co-crystals of UNC119 with an acylated Talpha N-terminal peptide at 2.0 A revealed that the lipid chain is buried deeply into UNC119's hydrophobic cavity. UNC119 bound Talpha-GTP, inhibiting its GTPase activity, thereby providing a stable UNC119-Talpha-GTP complex capable of diffusing from the inner segment back to the outer segment after light-induced translocation. UNC119 deletion in both mouse and C. elegans led to G protein mislocalization. Thus, UNC119 is a Galpha subunit cofactor essential for G protein trafficking in sensory cilia.

UNC119 is required for G protein trafficking in sensory neurons.,Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W Nat Neurosci. 2011 Jun 5. PMID:21642972^[3]

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

References

↑ Wright KJ, Baye LM, Olivier-Mason A, Mukhopadhyay S, Sang L, Kwong M, Wang W, Pretorius PR, Sheffield VC, Sengupta P, Slusarski DC, Jackson PK. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 2011 Nov 15;25(22):2347-60. doi: 10.1101/gad.173054.111. PMID:22085962 doi:10.1101/gad.173443.111
↑ Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W. UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci. 2011 Jun 5. PMID:21642972 doi:10.1038/nn.2835
↑ Zhang H, Constantine R, Vorobiev S, Chen Y, Seetharaman J, Huang YJ, Xiao R, Montelione GT, Gerstner CD, Davis MW, Inana G, Whitby FG, Jorgensen EM, Hill CP, Tong L, Baehr W. UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci. 2011 Jun 5. PMID:21642972 doi:10.1038/nn.2835

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3rbq"

@@ Line 1: / Line 1: @@
 ==Co-crystal structure of human UNC119 (retina gene 4) and an N-terminal Transducin-alpha mimicking peptide==
-<StructureSection load='3rbq' size='340' side='right' caption='[[3rbq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3rbq' size='340' side='right'caption='[[3rbq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rbq]] is a 12 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=3RBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RBQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rbq]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RBQ FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gqq|3gqq]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3gqq|3gqq]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNC119, RG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UNC119, RG4 ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rbq OCA], [http://pdbe.org/3rbq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rbq RCSB], [http://www.ebi.ac.uk/pdbsum/3rbq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rbq ProSAT]</span></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=3rbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rbq OCA], [https://pdbe.org/3rbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rbq RCSB], [https://www.ebi.ac.uk/pdbsum/3rbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rbq ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Idiopathic CD4 lymphocytopenia;Cone rod dystrophy. Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. [[http://www.uniprot.org/uniprot/GNAT1_HUMAN GNAT1_HUMAN]] Congenital stationary night blindness. The disease is caused by mutations affecting the gene represented in this entry.
+[[https://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Idiopathic CD4 lymphocytopenia;Cone rod dystrophy. Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. [[https://www.uniprot.org/uniprot/GNAT1_HUMAN GNAT1_HUMAN]] Congenital stationary night blindness. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells.<ref>PMID:22085962</ref> <ref>PMID:21642972</ref>  [[http://www.uniprot.org/uniprot/GNAT1_HUMAN GNAT1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
+[[https://www.uniprot.org/uniprot/U119A_HUMAN U119A_HUMAN]] Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Binds myristoylated NPHP3; however, in contrast to UNC119B, does not seem to play a major role in ciliary membrane localization of NPHP3. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells.<ref>PMID:22085962</ref> <ref>PMID:21642972</ref>  [[https://www.uniprot.org/uniprot/GNAT1_HUMAN GNAT1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Baehr, W]]
 [[Category: Constantine, R]]

3rbq

From Proteopedia

Revision as of 05:56, 15 June 2022

Co-crystal structure of human UNC119 (retina gene 4) and an N-terminal Transducin-alpha mimicking peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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