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Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
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Assembly of Signaling Complexes

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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Structure of Cadherins01:25

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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...

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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
10:05

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Published on: August 13, 2012

Structural basis for NHERF1 PDZ domain binding.

Tatyana Mamonova1, Maria Kurnikova, Peter A Friedman

  • 1Laboratory for G Protein-Coupled Receptor Biology, Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

Biochemistry
|March 21, 2012
PubMed
Summary
This summary is machine-generated.

The Na(+)/H(+) exchange regulatory factor-1 (NHERF1) scaffolding protein

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Published on: January 26, 2024

Area of Science:

  • Molecular biology
  • Biochemistry
  • Structural biology

Background:

  • Na(+)/H(+) exchange regulatory factor-1 (NHERF1) is a scaffolding protein with two PDZ domains.
  • NHERF1 interacts with parathyroid hormone receptor (PTHR), phosphate cotransporter (Npt2a), and β2-adrenergic receptor (β2-AR).
  • In its basal state, NHERF1 adopts a self-inhibited conformation.

Purpose of the Study:

  • To investigate the structural and biochemical basis of NHERF1 PDZ domain binding selectivity.
  • To understand the molecular mechanisms underlying NHERF1 interactions with its target proteins.

Main Methods:

  • Molecular dynamics (MD) simulations were employed.
  • Binding free energy (ΔG) calculations were performed for PDZ1 and PDZ2 interactions.
  • Comparison of binding energies for NHERF1 self-association and target protein interactions.

Main Results:

  • PDZ1 exhibits unique contacts that stabilize interactions with target ligands more than PDZ2.
  • Calculated binding free energies reveal competition between NHERF1 PDZ domains and target proteins.
  • PDZ2 binding to PTHR may disrupt NHERF1 self-inhibition, promoting an active conformation.

Conclusions:

  • NHERF1 PDZ domain binding selectivity is determined by specific structural contacts.
  • Interactions with PTHR, Npt2a, and β2-AR involve competitive binding mechanisms.
  • NHERF1's self-inhibited state can be overcome by interactions with specific target proteins, potentially regulating its function.