Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes Export

@article{citeulike:1849187, abstract = {Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded [beta] helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B{alpha} from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and complementation analyses reveal a conserved binding epitope for eEF1A that is required for normal cell growth, proliferation, and cell cycle progression. Structural differences between the ZPR1 domains contribute to the observed functional divergence and provide evidence for distinct modalities of interaction with eEF1A and survival motor neuron complexes. 10.1073/pnas.0704915104}, author = {Mishra, Ashwini K. and Gangwani, Laxman and Davis, Roger J. and Lambright, David G.}, citeulike-article-id = {1849187}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0704915104}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/104/35/13930}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17704259}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17704259}, day = {28}, doi = {10.1073/pnas.0704915104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {complex, domain, eukaryota, evolution, interaction, structure}, month = {August}, number = {35}, pages = {13930--13935}, posted-at = {2007-11-01 02:01:47}, priority = {3}, title = {Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes}, url = {http://dx.doi.org/10.1073/pnas.0704915104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1849187 L3 - citeulike-article-id:1849187 N2 - Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded [beta] helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B{alpha} from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and complementation analyses reveal a conserved binding epitope for eEF1A that is required for normal cell growth, proliferation, and cell cycle progression. Structural differences between the ZPR1 domains contribute to the observed functional divergence and provide evidence for distinct modalities of interaction with eEF1A and survival motor neuron complexes. 10.1073/pnas.0704915104 IS - 35 JF - Proceedings of the National Academy of Sciences EP - 13935 TI - Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes VL - 104 SP - 13930 KW - complex KW - domain KW - eukaryota KW - evolution KW - interaction KW - structure AU - Mishra, Ashwini AU - Gangwani, Laxman AU - Davis, Roger AU - Lambright, David PY - 2007/08/28/ UR - http://dx.doi.org/10.1073/pnas.0704915104 ER -