Structure of GABARAP in two conformations: Implications for GABAA receptor localization and tubulin binding Journal Article

  

Authors:	Coyle, J. E.; Qamar, S.; Rajashankar, K. R.; Nikolov, D. B.
Article Title:	Structure of GABARAP in two conformations: Implications for GABAA receptor localization and tubulin binding
Abstract:	GABARAP recognizes and binds the γ2 subunit of the GABAA receptor, interacts with microtubules and the N-ethyl maleimide sensitive factor, and is proposed to function in GABAA receptor trafficking and postsynaptic localization. We have determined the crystal structure of human GABARAP at 1.6 Å resolution. The structure comprises an N-terminal helical subdomain and a ubiquitin-like C-terminal domain. Structure-based mutational analysis demonstrates that the N-terminal subdomain is responsible for tubulin binding while the C-terminal domain contains the binding site for the GABAA. A second GABARAP crystal form was determined at 1.9 Å resolution and documents that GABARAP can self-associate in a head-to-tail manner. The structural details of this oligomerization reveal how GABARAP can both promote tubulin polymerization and facilitate GABAA receptor clustering.
Keywords:	controlled study; nonhuman; protein conformation; protein domain; protein function; protein localization; animal cell; animals; protein binding; molecular sequence data; sequence homology, amino acid; amino terminal sequence; polymerization; protein transport; adaptor proteins, signal transducing; binding protein; binding site; crystal structure; protein structure, tertiary; binding sites; protein subunit; protein structure; structure analysis; tubulin; microtubule; microtubules; oligomerization; polymers; microtubule-associated proteins; synaptic transmission; neural inhibition; receptors, gaba-a; humans; priority journal; article; 4 aminobutyric acid receptor; n ethylmaleimide; postsynaptic membrane; synaptic membranes
Journal Title:	Neuron
Volume:	33
Issue:	1
ISSN:	0896-6273
Publisher:	Cell Press
Date Published:	2002-01-03
Start Page:	63
End Page:	74
Language:	English
DOI:	10.1016/s0896-6273(01)00558-x
PUBMED:	11779480
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0037012104&partnerID=40&md5=7b52022937532c8ecad5eae6e0ff4b7a
Notes:	Export Date: 14 November 2014 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/66474