8jj9

From Proteopedia

(Difference between revisions)

Current revision

Human FAM91A1 N terminal domain in complex with TBC1D23

Structural highlights

8jj9 is a 4 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 2.51Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TBC23_HUMAN The disease is caused by mutations affecting the gene represented in this entry.

Function

TBC23_HUMAN Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity).[UniProtKB:Q8K0F1]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.

FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.,Zhao L, Deng H, Yang Q, Tang Y, Zhao J, Li P, Zhang S, Yong X, Li T, Billadeau DD, Jia D Proc Natl Acad Sci U S A. 2023 Nov 7;120(45):e2309910120. doi: , 10.1073/pnas.2309910120. Epub 2023 Oct 30. PMID:37903274^[4]

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

References

↑ Ivanova EL, Mau-Them FT, Riazuddin S, Kahrizi K, Laugel V, Schaefer E, de Saint Martin A, Runge K, Iqbal Z, Spitz MA, Laura M, Drouot N, Gerard B, Deleuze JF, de Brouwer APM, Razzaq A, Dollfus H, Assir MZ, Nitchke P, Hinckelmann MV, Ropers H, Riazuddin S, Najmabadi H, van Bokhoven H, Chelly J. Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development. Am J Hum Genet. 2017 Sep 7;101(3):428-440. doi: 10.1016/j.ajhg.2017.07.010. Epub , 2017 Aug 17. PMID:28823707 doi:http://dx.doi.org/10.1016/j.ajhg.2017.07.010
↑ Shin JJH, Gillingham AK, Begum F, Chadwick J, Munro S. TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at the trans-Golgi. Nat Cell Biol. 2017 Dec;19(12):1424-1432. doi: 10.1038/ncb3627. Epub 2017 Oct 30. PMID:29084197 doi:http://dx.doi.org/10.1038/ncb3627
↑ Navarro Negredo P, Edgar JR, Manna PT, Antrobus R, Robinson MS. The WDR11 complex facilitates the tethering of AP-1-derived vesicles. Nat Commun. 2018 Feb 9;9(1):596. doi: 10.1038/s41467-018-02919-4. PMID:29426865 doi:http://dx.doi.org/10.1038/s41467-018-02919-4
↑ Zhao L, Deng H, Yang Q, Tang Y, Zhao J, Li P, Zhang S, Yong X, Li T, Billadeau DD, Jia D. FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH. Proc Natl Acad Sci U S A. 2023 Nov 7;120(45):e2309910120. PMID:37903274 doi:10.1073/pnas.2309910120

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/8jj9"

Categories: Homo sapiens | Large Structures | Deng HQ | Jia D | Zhang ST

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jj9 is ON HOLD  until 2025-05-29
+==Human FAM91A1 N terminal domain in complex with TBC1D23==
+<StructureSection load='8jj9' size='340' side='right'caption='[[8jj9]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jj9]] is a 4 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=8JJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JJ9 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.51&#8491;</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=8jj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jj9 OCA], [https://pdbe.org/8jj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jj9 RCSB], [https://www.ebi.ac.uk/pdbsum/8jj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jj9 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/TBC23_HUMAN TBC23_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/TBC23_HUMAN TBC23_HUMAN] Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity).[UniProtKB:Q8K0F1]<ref>PMID:28823707</ref> <ref>PMID:29084197</ref> <ref>PMID:29426865</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.
-Authors: Deng, H.Q., Zhang, S.T., Jia, D.
+FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.,Zhao L, Deng H, Yang Q, Tang Y, Zhao J, Li P, Zhang S, Yong X, Li T, Billadeau DD, Jia D Proc Natl Acad Sci U S A. 2023 Nov 7;120(45):e2309910120. doi: , 10.1073/pnas.2309910120. Epub 2023 Oct 30. PMID:37903274<ref>PMID:37903274</ref>
-Description: Human FAM91A1 N terminal domain in complex with TBC1D23
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Deng, H.Q]]
+<div class="pdbe-citations 8jj9" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, S.T]]
+== References ==
-[[Category: Jia, D]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Deng HQ]]
+[[Category: Jia D]]
+[[Category: Zhang ST]]

8jj9

From Proteopedia

Current revision

Human FAM91A1 N terminal domain in complex with TBC1D23

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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