Related Experiment Video

Updated: Nov 8, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

4.3K

Phosphopeptide interactions of the Nbs1 N-terminal FHA-BRCT1/2 domains

Kyungmin Kim1, Thomas W Kirby1, Lalith Perera1

  • 1Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.

Scientific Reports
|April 28, 2021
PubMed

Insights

Human Nbs1 protein, crucial for DNA repair, binds to phosphopeptides via its BRCT1/2 domains. This study reveals Nbs1

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Protein Structure-Function Relationships

Background:

  • Human Nbs1 is a key component of the MRN complex, essential for DNA double-strand break (DSB) repair.
  • The N-terminal FHA-BRCT1/2 sequence of Nbs1 mediates interactions with various phosphopeptide binding partners.
  • Nbs1 localization and function are regulated by interactions with MDC1 and CtIP, influencing DNA resection.

Purpose of the Study:

  • To investigate the phosphopeptide binding characteristics of the Nbs1 BRCT1/2 domains.
  • To elucidate the structural basis for Nbs1's interactions with its binding partners.
  • To identify specific phosphopeptide motifs recognized by Nbs1 BRCT1/2.

Main Methods:

  • Molecular modeling approach to study the Nbs1 BRCT1/2 domains.
  • Structural homology comparison with tandem TopBP1 BRCT7/8 domains.
  • In silico analysis of phosphopeptide binding preferences and affinity.

Main Results:

  • The modeled Nbs1 BRCT1/2 domains exhibit structural homology to TopBP1 BRCT7/8.
  • Nbs1 BRCT1/2 shows low selectivity for pSer/pThr, prefers cationic residues at +2, and hydrophobic residues at +3/+4.
  • CtIP phosphopeptides (pSer347, pThr847) and rodent XRCC1 SDT motif were identified as high/low affinity ligands.

Conclusions:

  • The study provides structural insights into Nbs1 BRCT1/2 phosphopeptide binding.
  • Nbs1's binding characteristics explain interactions with CtIP and XRCC1.
  • Understanding these interactions is crucial for comprehending DNA repair regulation.

More Related Videos

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions10:58

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

Published on: July 27, 2017

9.6K
Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET12:07

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET

Published on: October 9, 2021

3.6K

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.1K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
9.4K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
13.5K
Protein-protein Interfaces02:04

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.1K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
14.0K