6UBH

Structure of the MM7 Erbin PDZ variant in complex with a high-affinity peptide

6UBH の概要

• エントリーDOI: 10.2210/pdb6ubh/pdb
• 関連するPDBエントリー: 1N7T 6Q0M 6Q0N 6Q0U
• 分子名称: Erbin, peptide, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: phage display, directed evolution, -2 position, specificity, phage library, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 45155.94

構造登録者

Singer, A.U.,Teyra, J.,McLaughlin, M.,Ernst, A.,Sicheri, F.,Sidhu, S.S. (登録日: 2019-09-11, 公開日: 2020-07-29, 最終更新日: 2023-10-11)

主引用文献

Teyra, J.,McLaughlin, M.,Singer, A.,Kelil, A.,Ernst, A.,Sicheri, F.,Sidhu, S.S.
Comprehensive Assessment of the Relationship Between Site -2 Specificity and Helix alpha 2 in the Erbin PDZ Domain.
J.Mol.Biol., 433:167115-167115, 2021

PubMed Abstract: PDZ domains are key players in signalling pathways. These modular domains generally recognize short linear C-terminal stretches of sequences in proteins that organize the formation of complex multi-component assemblies. The development of new methodologies for the characterization of the molecular principles governing these interactions is critical to fully understand the functional diversity of the family and to elucidate biological functions for family members. Here, we applied an in vitro evolution strategy to explore comprehensively the capacity of PDZ domains for specific recognition of different amino acids at a key position in C-terminal peptide ligands. We constructed a phage-displayed library of the Erbin PDZ domain by randomizing the binding site and adjacent residues, which are all contained in helix α2, and we selected for variants binding to a panel of peptides representing all possible position residues. This approach generated insights into the basis for the common natural class I and II specificities, demonstrated an alternative basis for a rare natural class III specificity for Asp, and revealed a novel specificity for Arg that has not been reported in natural PDZ domains. A structure of a PDZ-peptide complex explained the minimum requirement for switching specificity from class I ligands containing Thr/Ser to class II ligands containing hydrophobic residues at position. A second structure explained the molecular basis for the specificity for ligands containing Arg. Overall, the evolved PDZ variants greatly expand our understanding of site specificities and the variants themselves may prove useful as building blocks for synthetic biology.

PubMed: 34171344
DOI: 10.1016/j.jmb.2021.167115

実験手法

X-RAY DIFFRACTION (1.8 Å)