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
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
DOI: 10.1038/s41467-020-18773-2
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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