4NXR

Crystal Structure of T-cell Lymphoma Invasion and Metastasis-1 PDZ Domain Quadruple Mutant (QM) in Complex With Neurexin-1 Peptide

4NXR の概要

• エントリーDOI: 10.2210/pdb4nxr/pdb
• 関連するPDBエントリー: 3KZD 3KZE 4GVC 4GVD 4NXP 4NXQ
• 分子名称: T-lymphoma invasion and metastasis-inducing protein 1, Neurexin-2-beta Peptide, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: beta barrel fold protein, pdz domain, peptide binding, specificity mutant, scaffold signaling protein for cell adhesion and cell junction, signaling domain, signaling protein-peptide complex, signaling protein/peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell junction: Q13009; Membrane ; Single-pass type I membrane protein : P58401
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11742.17

構造登録者

Liu, X.,Speckhard, D.C.,Shepherd, T.R.,Hengel, S.R.,Fuentes, E.J. (登録日: 2013-12-09, 公開日: 2015-05-13, 最終更新日: 2023-09-20)

主引用文献

Liu, X.,Speckhard, D.C.,Shepherd, T.R.,Sun, Y.J.,Hengel, S.R.,Yu, L.,Fowler, C.A.,Gakhar, L.,Fuentes, E.J.
Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions.
Structure, 24:2053-2066, 2016

PubMed Abstract: Conformational dynamics has an established role in enzyme catalysis, but its contribution to ligand binding and specificity is largely unexplored. Here we used the Tiam1 PDZ domain and an engineered variant (QM PDZ) with broadened specificity to investigate the role of structure and conformational dynamics in molecular recognition. Crystal structures of the QM PDZ domain both free and bound to ligands showed structural features central to binding (enthalpy), while nuclear-magnetic-resonance-based methyl relaxation experiments and isothermal titration calorimetry revealed that conformational entropy contributes to affinity. In addition to motions relevant to thermodynamics, slower microsecond to millisecond switching was prevalent in the QM PDZ ligand-binding site consistent with a role in ligand specificity. Our data indicate that conformational dynamics plays distinct and fundamental roles in tuning the affinity (conformational entropy) and specificity (excited-state conformations) of molecular interactions. More broadly, our results have important implications for the evolution, regulation, and design of protein-ligand interactions.

PubMed: 27998539
DOI: 10.1016/j.str.2016.08.019

実験手法

X-RAY DIFFRACTION (1.9 Å)