5HET

The third PDZ domain from the synaptic protein PSD-95 (G330T mutant)

5HET の概要

• エントリーDOI: 10.2210/pdb5het/pdb
• 関連するPDBエントリー: 1BFE 5HDY 5HEB 5HED 5HEY 5HF1 5HF4 5HFB 5HFC 5HFD 5HFE 5HFF
• 分子名称: Disks large homolog 4 (2 entities in total)
• 機能のキーワード: pdz, glgf, dhr, adhesion, synapse, synaptic density, peptide-binding domain, peptide binding protein
• 由来する生物種: Rattus norvegicus (Rat)
• 細胞内の位置: Cell membrane; Peripheral membrane protein: P31016
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12782.12

構造登録者

White, K.I.,Raman, A.S.,Ranganathan, R. (登録日: 2016-01-06, 公開日: 2016-11-16, 最終更新日: 2023-09-27)

主引用文献

Raman, A.S.,White, K.I.,Ranganathan, R.
Origins of Allostery and Evolvability in Proteins: A Case Study.
Cell(Cambridge,Mass.), 166:468-480, 2016

PubMed Abstract: Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-binding site. These mutations provide a functional link between ligand classes and demonstrate the principle of "conditional neutrality" in mediating evolutionary adaptation. Structures show that class-bridging mutations work allosterically to open up conformational plasticity at the active site, permitting novel functions while retaining existing function. More generally, the class-bridging phenotype arises from mutations in an evolutionarily conserved network of coevolving amino acids in the PDZ family (the sector) that connects the active site to distant surface sites. These findings introduce the concept that allostery in proteins could have its origins not in protein function but in the capacity to adapt.

PubMed: 27321669
DOI: 10.1016/j.cell.2016.05.047

実験手法

X-RAY DIFFRACTION (2.001 Å)