High affinity binding of the receptor-associated protein D1D2 domains with the LDL receptor-related protein (LRP1) involves bivalent complex formation: Critical roles of lysine 60 and 191. [Molecular Biophysics]

July 11th, 2016 by Prasad, J. M., Young, P. A., Strickland, D. K.

The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three domain protein that contains two high affinity binding sites for LRP1: one located within domains 1 and 2, and one located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2/LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor.
  • Posted in Journal of Biological Chemistry, Publications
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Pistol ribozyme adopts a pseudoknot fold facilitating site-specific in-line cleavage

July 11th, 2016 by Aiming Ren

Nature Chemical Biology 12, 702 (2016). doi:10.1038/nchembio.2125

Authors: Aiming Ren, Nikola Vušurović, Jennifer Gebetsberger, Pu Gao, Michael Juen, Christoph Kreutz, Ronald Micura & Dinshaw J Patel

  • Posted in Nat Chem Biol, Publications
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A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines

July 11th, 2016 by Yuji Ogura

Nature Chemical Biology 12, 669 (2016). doi:10.1038/nchembio.2127

Authors: Yuji Ogura, William H Parsons, Siddhesh S Kamat & Benjamin F Cravatt

More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remained mysterious. Here, we use activity-based protein profiling to identify the poorly characterized serine hydrolase PLA2G4E as a mouse brain Ca-NAT and show that this enzyme generates NAPEs and NAEs in mammalian cells.

  • Posted in Nat Chem Biol, Publications
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Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor

July 11th, 2016 by Alem W Kahsai

Nature Chemical Biology 12, 709 (2016). doi:10.1038/nchembio.2126

Authors: Alem W Kahsai, James W Wisler, Jungmin Lee, Seungkirl Ahn, Thomas J Cahill III, S Moses Dennison, Dean P Staus, Alex R B Thomsen, Kara M Anasti, Biswaranjan Pani, Laura M Wingler, Hemant Desai, Kristin M Bompiani, Ryan T Strachan, Xiaoxia Qin, S Munir Alam, Bruce A Sullenger & Robert J Lefkowitz

  • Posted in Nat Chem Biol, Publications
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Tbx16 regulates hox gene activation in mesodermal progenitor cells

July 4th, 2016 by Alexander Y Payumo

Nature Chemical Biology 12, 694 (2016). doi:10.1038/nchembio.2124

Authors: Alexander Y Payumo, Lindsey E McQuade, Whitney J Walker, Sayumi Yamazoe & James K Chen

ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity

July 4th, 2016 by Baoen Chen

Nature Chemical Biology 12, 686 (2016). doi:10.1038/nchembio.2119

Authors: Baoen Chen, Baohui Zheng, Michael DeRan, Gopala K Jarugumilli, Jianjun Fu, Yang S Brooks & Xu Wu

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

July 4th, 2016 by Anja F Hohmann

Nature Chemical Biology 12, 672 (2016). doi:10.1038/nchembio.2115

Authors: Anja F Hohmann, Laetitia J Martin, Jessica L Minder, Jae-Seok Roe, Junwei Shi, Steffen Steurer, Gerd Bader, Darryl McConnell, Mark Pearson, Thomas Gerstberger, Teresa Gottschamel, Diane Thompson, Yutaka Suzuki, Manfred Koegl & Christopher R Vakoc

  • Posted in Nat Chem Biol, Publications
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A reactivity-based probe of the intracellular labile ferrous iron pool

July 4th, 2016 by Benjamin Spangler

Nature Chemical Biology 12, 680 (2016). doi:10.1038/nchembio.2116

Authors: Benjamin Spangler, Charles W Morgan, Shaun D Fontaine, Mark N Vander Wal, Christopher J Chang, James A Wells & Adam R Renslo

  • Posted in Nat Chem Biol, Publications
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Identification of Cyanobacteriochromes Detecting Far-Red Light

July 2nd, 2016 by Nathan C. Rockwell, Shelley S. Martin and J. Clark Lagarias

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Biochemistry
DOI: 10.1021/acs.biochem.6b00299

Benchmarking of TALE- and CRISPR/dCas9-Based Transcriptional Regulators in Mammalian Cells for the Construction of Synthetic Genetic Circuits

June 28th, 2016 by Tina Lebar and Roman Jerala

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.5b00259
  • Posted in ACS Synthetic Biology, Publications
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