Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
Autor: | J. Paul Luzio, Brett M. Collins, Nicholas A. Bright, Joel B. Dacks, James S. Swarbrick, Lena Wartosch, Harriet Crawley-Snowdon, Ji-Chun Yang, Luther J. Davis, Nathan R. Zaccai, Lauren P. Jackson, David J. Owen, Matthew N.J. Seaman, David Neuhaus, Emily K. Herman |
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Přispěvatelé: | Yang, Ji-Chun [0000-0003-1933-5372], Herman, Emily K. [0000-0002-5327-0755], Bright, Nicholas A. [0000-0002-2791-6727], Collins, Brett M. [0000-0002-6070-3774], Jackson, Lauren P. [0000-0002-3705-6126], Seaman, Matthew N. J. [0000-0001-9916-3245], Luzio, J. Paul [0000-0003-3912-9760], Dacks, Joel B. [0000-0003-4520-5694], Neuhaus, David [0000-0002-8561-7485], Owen, David J. [0000-0002-8351-6322], Apollo - University of Cambridge Repository, Herman, Emily K [0000-0002-5327-0755], Bright, Nicholas A [0000-0002-2791-6727], Collins, Brett M [0000-0002-6070-3774], Jackson, Lauren P [0000-0002-3705-6126], Seaman, Matthew NJ [0000-0001-9916-3245], Luzio, J Paul [0000-0003-3912-9760], Dacks, Joel B [0000-0003-4520-5694], Owen, David J [0000-0002-8351-6322] |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Models
Molecular 0301 basic medicine 631/45 631/535/878/1263 Magnetic Resonance Spectroscopy GTPase-activating protein Retromer Protein Conformation Endosome 101 Science Protein subunit Vesicular Transport Proteins General Physics and Astronomy Endosomes Biochemistry General Biochemistry Genetics and Molecular Biology Evolution Molecular 03 medical and health sciences 0302 clinical medicine Protein structure Guanine Nucleotide Exchange Factors Humans 82/103 Cysteine lcsh:Science Zinc finger Multidisciplinary Chemistry Cryoelectron Microscopy GTPase-Activating Proteins article Zinc Fingers General Chemistry Cell biology 631/80/313/1776 Zinc 030104 developmental biology VPS29 Multiprotein Complexes 9 lcsh:Q Guanine nucleotide exchange factor Solution-state NMR 030217 neurology & neurosurgery HeLa Cells |
Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
ISSN: | 2041-1723 |
Popis: | Funder: Discovery Grants from the Natural Sciences and Engineering Research Council of Canada (RES0043758, RES0046091) VARP and TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes. Using an NMR/X-ray approach, we determined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Zn++ microdomain, which we term a Zn-fingernail, two of which are present in VARP. Mutations that abolish VPS29:VARP binding inhibit trafficking from endosomes to the cell surface. We show that VARP and TBC1D5 bind the same site on VPS29 and can compete for binding VPS29 in vivo. The relative disposition of VPS29s in hetero-hexameric, membrane-attached, retromer arches indicates that VARP will prefer binding to assembled retromer coats through simultaneous binding of two VPS29s. The TBC1D5:VPS29 interaction is over one billion years old but the Zn-fingernail appears only in VARP homologues in the lineage directly giving rise to animals at which point the retromer/VARP/TBC1D5 regulatory network became fully established. |
Databáze: | OpenAIRE |
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