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Title: Structural and Functional Analysis of Saccharomyces Cerevisiae Mob1

Abstract

The Mob proteins function as activator subunits for the Dbf2/Dbf20 family of protein kinases. Human and Xenopus Mob1 protein structures corresponding to the most conserved C-terminal core, but lacking the variable N-terminal region, have been reported and provide a framework for understanding the mechanism of Dbf2/Dbf20 regulation. Here, we report the 2.0 {angstrom} X-ray crystal structure of Saccharomyces cerevisiae Mob1 containing both the conserved C-terminal core and the variable N-terminal region. Within the N-terminal region, three novel structural elements are observed; namely, an {alpha}-helix denoted H0, a strand-like element denoted S0 and a short {beta} strand denoted S-1. Helix H0 associates in an intermolecular manner with a second Mob1 molecule to form a Mob1 homodimer. Strand S0 binds to the core domain in an intramolecular manner across a putative Dbf2 binding site mapped by Mob1 temperature-sensitive alleles and NMR binding experiments. In vivo functional analysis demonstrates that Mob1 mutants that target helix H0 or its reciprocal binding site are biologically compromised. The N-terminal region of Mob1 thus contains structural elements that are functionally important.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930112
Report Number(s):
BNL-80756-2008-JA
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US200822%%1325
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Molecular Biology; Journal Volume: 362
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; ELEMENTS; FUNCTIONAL ANALYSIS; FUNCTIONS; HUMAN POPULATIONS; IN VIVO; MOLECULES; MUTANTS; NUCLEAR MAGNETIC RESONANCE; PHOSPHOTRANSFERASES; PROTEIN STRUCTURE; PROTEINS; SACCHAROMYCES CEREVISIAE; national synchrotron light source

Citation Formats

Mrkobrada,S., Boucher, L., Tyers, D., and Sicheri, F. Structural and Functional Analysis of Saccharomyces Cerevisiae Mob1. United States: N. p., 2006. Web. doi:10.1016/j.jmb.2006.07.007.
Mrkobrada,S., Boucher, L., Tyers, D., & Sicheri, F. Structural and Functional Analysis of Saccharomyces Cerevisiae Mob1. United States. doi:10.1016/j.jmb.2006.07.007.
Mrkobrada,S., Boucher, L., Tyers, D., and Sicheri, F. Sun . "Structural and Functional Analysis of Saccharomyces Cerevisiae Mob1". United States. doi:10.1016/j.jmb.2006.07.007.
@article{osti_930112,
title = {Structural and Functional Analysis of Saccharomyces Cerevisiae Mob1},
author = {Mrkobrada,S. and Boucher, L. and Tyers, D. and Sicheri, F.},
abstractNote = {The Mob proteins function as activator subunits for the Dbf2/Dbf20 family of protein kinases. Human and Xenopus Mob1 protein structures corresponding to the most conserved C-terminal core, but lacking the variable N-terminal region, have been reported and provide a framework for understanding the mechanism of Dbf2/Dbf20 regulation. Here, we report the 2.0 {angstrom} X-ray crystal structure of Saccharomyces cerevisiae Mob1 containing both the conserved C-terminal core and the variable N-terminal region. Within the N-terminal region, three novel structural elements are observed; namely, an {alpha}-helix denoted H0, a strand-like element denoted S0 and a short {beta} strand denoted S-1. Helix H0 associates in an intermolecular manner with a second Mob1 molecule to form a Mob1 homodimer. Strand S0 binds to the core domain in an intramolecular manner across a putative Dbf2 binding site mapped by Mob1 temperature-sensitive alleles and NMR binding experiments. In vivo functional analysis demonstrates that Mob1 mutants that target helix H0 or its reciprocal binding site are biologically compromised. The N-terminal region of Mob1 thus contains structural elements that are functionally important.},
doi = {10.1016/j.jmb.2006.07.007},
journal = {Journal of Molecular Biology},
number = ,
volume = 362,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}
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  • No abstract prepared.