Structural highlights
Function
NBP2_YEAST Negatively regulates the high-osmolarity glycerol (HOG) pathway through its negative regulation of the HOG1 kinase activity. Mediates the binding between the PTC1 phosphatase and the PBS2 MAP/ERK kinase (MEK). With PTC1, regulates endoplasmic reticulum inheritance through the cell wall integrity (CWI) MAPK pathway by modulating the MAPK, SLT2.[1] [2] [3]
Publication Abstract from PubMed
The yeast Nbp2p SH3 and Bem1p SH3b domains bind certain target peptides with similar high affinities, yet display vastly different affinities for other targets. To investigate this unusual behavior, we have solved the structure of the Nbp2p SH3-Ste20 peptide complex and compared it with the previously determined structure of the Bem1p SH3b bound to the same peptide. Although the Ste20 peptide interacts with both domains in a structurally similar manner, extensive in vitro studies with domain and peptide mutants revealed large variations in interaction strength across the binding interface of the two complexes. Whereas the Nbp2p SH3 made stronger contacts with the peptide core RXXPXXP motif, the Bem1p SH3b domain made stronger contacts with residues flanking the core motif. Remarkably, this modulation of local binding energetics can explain the distinct and highly nuanced binding specificities of these two domains.
Distinct Peptide Binding Specificities of Src Homology 3 (SH3) Protein Domains Can Be Determined by Modulation of Local Energetics across the Binding Interface.,Gorelik M, Davidson AR J Biol Chem. 2012 Mar 16;287(12):9168-77. Epub 2012 Jan 25. PMID:22277653[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ohkuni K, Okuda A, Kikuchi A. Yeast Nap1-binding protein Nbp2p is required for mitotic growth at high temperatures and for cell wall integrity. Genetics. 2003 Oct;165(2):517-29. PMID:14573466
- ↑ Mapes J, Ota IM. Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK pathway. EMBO J. 2004 Jan 28;23(2):302-11. Epub 2003 Dec 18. PMID:14685261 doi:http://dx.doi.org/10.1038/sj.emboj.7600036
- ↑ Du Y, Walker L, Novick P, Ferro-Novick S. Ptc1p regulates cortical ER inheritance via Slt2p. EMBO J. 2006 Oct 4;25(19):4413-22. Epub 2006 Sep 14. PMID:16977319 doi:http://dx.doi.org/10.1038/sj.emboj.7601319
- ↑ Gorelik M, Davidson AR. Distinct Peptide Binding Specificities of Src Homology 3 (SH3) Protein Domains Can Be Determined by Modulation of Local Energetics across the Binding Interface. J Biol Chem. 2012 Mar 16;287(12):9168-77. Epub 2012 Jan 25. PMID:22277653 doi:10.1074/jbc.M111.330753
