8p0x

From Proteopedia

Structure of the human Commander complex Retriever Subcomplex

PDB ID 8p0x

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Structural highlights

8p0x is a 5 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:	Electron Microscopy, Resolution 7.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CCD93_HUMAN Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1 (PubMed:25355947, PubMed:28892079). Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes and is dependent on its interaction with WASHC2C (PubMed:25355947).^[1] ^[2] (Microbial infection) The CCC complex, in collaboration with the heterotrimeric retriever complex, mediates the exit of human papillomavirus to the cell surface.^[3]

Publication Abstract from PubMed

The Commander complex, a 16-protein assembly, plays multiple roles in cell homeostasis, cell cycle and immune response. It consists of copper-metabolism Murr1 domain proteins (COMMD1-10), coiled-coil domain-containing proteins (CCDC22 and CCDC93), DENND10 and the Retriever subcomplex (VPS26C, VPS29 and VPS35L), all expressed ubiquitously in the body and linked to various diseases. Here, we report the structure and key interactions of the endogenous human Commander complex by cryogenic-electron microscopy and mass spectrometry-based proteomics. The complex consists of a stable core of COMMD1-10 and an effector containing DENND10 and Retriever, scaffolded together by CCDC22 and CCDC93. We establish the composition of Commander and reveal major interaction interfaces. These findings clarify its roles in intracellular transport, and uncover a strong association with cilium assembly, and centrosome and centriole functions.

Structure and interactions of the endogenous human Commander complex.,Laulumaa S, Kumpula EP, Huiskonen JT, Varjosalo M Nat Struct Mol Biol. 2024 Jun;31(6):925-938. doi: 10.1038/s41594-024-01246-1. , Epub 2024 Mar 8. PMID:38459129^[4]

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

References

↑ Phillips-Krawczak CA, Singla A, Starokadomskyy P, Deng Z, Osborne DG, Li H, Dick CJ, Gomez TS, Koenecke M, Zhang JS, Dai H, Sifuentes-Dominguez LF, Geng LN, Kaufmann SH, Hein MY, Wallis M, McGaughran J, Gecz J, Sluis Bv, Billadeau DD, Burstein E. COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Mol Biol Cell. 2015 Jan 1;26(1):91-103. PMID:25355947 doi:10.1091/mbc.E14-06-1073
↑ McNally KE, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D, Langton P, Pearson N, Danson CM, Nägele H, Morris LL, Singla A, Overlee BL, Heesom KJ, Sessions R, Banks L, Collins BM, Berger I, Billadeau DD, Burstein E, Cullen PJ. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017 Oct;19(10):1214-1225. PMID:28892079 doi:10.1038/ncb3610
↑ McNally KE, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D, Langton P, Pearson N, Danson CM, Nägele H, Morris LL, Singla A, Overlee BL, Heesom KJ, Sessions R, Banks L, Collins BM, Berger I, Billadeau DD, Burstein E, Cullen PJ. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017 Oct;19(10):1214-1225. PMID:28892079 doi:10.1038/ncb3610
↑ Laulumaa S, Kumpula EP, Huiskonen JT, Varjosalo M. Structure and interactions of the endogenous human Commander complex. Nat Struct Mol Biol. 2024 Jun;31(6):925-938. PMID:38459129 doi:10.1038/s41594-024-01246-1