[NMR paper] Solution NMR Structure of the SH3 Domain of Human Caskin1 Validates the Lack of a Typical Peptide Binding Groove and Supports a Role in Lipid Mediator Binding.
Solution NMR Structure of the SH3 Domain of Human Caskin1 Validates the Lack of a Typical Peptide Binding Groove and Supports a Role in Lipid Mediator Binding.
Related ArticlesSolution NMR Structure of the SH3 Domain of Human Caskin1 Validates the Lack of a Typical Peptide Binding Groove and Supports a Role in Lipid Mediator Binding.
Cells. 2021 Jan 16;10(1):
Authors: T?ke O, Koprivanacz K, Radnai L, Mer? B, Juhász T, Liliom K, Buday L
Abstract
SH3 domains constitute an important class of protein modules involved in a variety of cellular functions. They participate in protein-protein interactions via their canonical ligand binding interfaces composed of several evolutionarily conserved aromatic residues forming binding grooves for typical (PxxP) and atypical (PxxxPR, RxxK, RKxxY) binding motifs. The calcium/calmodulin-dependent serine protein kinase (CASK)-interacting protein 1, or Caskin1, a multidomain scaffold protein regulating the cortical actin filaments, is enriched in neural synapses in mammals. Based on its known interaction partners and knock-out animal studies, Caskin1 may play various roles in neural function and it is thought to participate in several pathological processes of the brain. Caskin1 has a single, atypical SH3 domain in which key aromatic residues are missing from the canonical binding groove. No protein interacting partner for this SH3 domain has been identified yet. Nevertheless, we have recently demonstrated the specific binding of this SH3 domain to the signaling lipid mediator lysophospatidic acid (LPA) in vitro. Here we report the solution NMR structure of the human Caskin1 SH3 domain and analyze its structural features in comparison with other SH3 domains exemplifying different strategies in target selectivity. The key differences revealed by our structural study show that the canonical binding groove found in typical SH3 domains accommodating proline-rich motifs is missing in Caskin1 SH3, most likely excluding a bona fide protein target for the domain. The LPA binding site is distinct from the altered protein binding groove. We conclude that the SH3 domain of Caskin1 might mediate the association of Caskin1 with membrane surfaces with locally elevated LPA content.
[NMR paper] Solution NMR Structure and Histone Binding of the PHD Domain of Human MLL5.
Solution NMR Structure and Histone Binding of the PHD Domain of Human MLL5.
Related Articles Solution NMR Structure and Histone Binding of the PHD Domain of Human MLL5.
PLoS One. 2013;8(10):e77020
Authors: Lemak A, Yee A, Wu H, Yap D, Zeng H, Dombrovski L, Houliston S, Aparicio S, Arrowsmith CH
Abstract
Mixed Lineage Leukemia 5 (MLL5) is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. In addition to its catalytic domain, MLL5 contains a PHD finger domain, a protein module that...
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Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25.
Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25.
Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25.
J Struct Funct Genomics. 2011 Jul 23;
Authors: Eletsky A, Ruyechan WT, Xiao R, Acton TB, Montelione GT, Szyperski T
The solution NMR structure of protein MED25(391-543), comprising the activator interacting domain (ACID) of subunit 25 of the human mediator, is presented along with the measurement of...
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07-26-2011 09:30 PM
[NMR paper] NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein
NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells.
Related Articles NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells.
Biochemistry. 2004 Feb 24;43(7):1854-61
Authors: Rosal R, Pincus MR, Brandt-Rauf PW, Fine RL, Michl J, Wang H
We have recently found that a peptide from the mdm-2 binding domain of the p53 protein induced rapid membranolytic necrosis of a variety of different human...
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11-24-2010 09:25 PM
[NMR paper] NMR solution structure of the receptor binding domain of human alpha(2)-macroglobulin
NMR solution structure of the receptor binding domain of human alpha(2)-macroglobulin.
Related Articles NMR solution structure of the receptor binding domain of human alpha(2)-macroglobulin.
J Biol Chem. 2000 Jan 14;275(2):1089-94
Authors: Huang W, Dolmer K, Liao X, Gettins PG
Human alpha(2)-macroglobulin-proteinase complexes bind to their receptor, the low density lipoprotein receptor-related protein (LRP), through a discrete 138-residue C-terminal receptor binding domain (RBD), which also binds to the beta-amyloid peptide. We have used NMR...
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11-18-2010 09:15 PM
NMR structure of the human Mediator MED25 ACID domain.
NMR structure of the human Mediator MED25 ACID domain.
Related Articles NMR structure of the human Mediator MED25 ACID domain.
J Struct Biol. 2010 Oct 22;
Authors: Bontems F, Verger A, Dewitte F, Lens Z, Baert JL, Ferreira E, de Launoit Y, Sizun C, Guittet E, Villeret V, Monté D
MED25 (ARC92/ACID1) is a 747 residues subunit specific to higher eukaryote Mediator complex, an essential component of the RNA polymerase II general transcriptional machinery. MED25 is a target of the Herpes simplex virus transactivator protein VP16. MED25 interacts...
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[NMR paper] NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (
NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (type 1) Rev.
Related Articles NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (type 1) Rev.
Biochemistry. 1995 Jul 4;34(26):8242-9
Authors: Scanlon MJ, Fairlie DP, Craik DJ, Englebretsen DR, West ML
NMR spectroscopy has been used to solve the three-dimensional solution structure of a minimal RNA-binding domain of the Rev protein from the human immunodeficiency virus (type 1), an essential regulatory protein for viral...
Solution NMR Structure of the SH3 Domain of Human Caskin1 Validates the Lack of a Typical Peptide Binding Groove and Supports a Role in Lipid Mediator Binding.
Linear Mode
