6PKD

Myocilin OLF mutant N428D/D478H

6PKD の概要

• エントリーDOI: 10.2210/pdb6pkd/pdb
• 分子名称: Myocilin, SODIUM ION (3 entities in total)
• 機能のキーワード: propeller, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62488.03

構造登録者

Lieberman, R.L.,Hill, S.E. (登録日: 2019-06-29, 公開日: 2019-09-11, 最終更新日: 2024-11-06)

主引用文献

Hill, S.E.,Cho, H.,Raut, P.,Lieberman, R.L.
Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices.
Acta Crystallogr D Struct Biol, 75:817-824, 2019

PubMed Abstract: Olfactomedins are a family of modular proteins found in multicellular organisms that all contain five-bladed β-propeller olfactomedin (OLF) domains. In support of differential functions for the OLF propeller, the available crystal structures reveal that only some OLF domains harbor an internal calcium-binding site with ligands derived from a triad of residues. For the myocilin OLF domain (myoc-OLF), ablation of the ion-binding site (triad Asp, Asn, Asp) by altering the coordinating residues affects the stability and overall structure, in one case leading to misfolding and glaucoma. Bioinformatics analysis reveals a variety of triads with possible ion-binding characteristics lurking in OLF domains in invertebrate chordates such as Arthropoda (Asp-Glu-Ser), Nematoda (Asp-Asp-His) and Echinodermata (Asp-Glu-Lys). To test ion binding and to extend the observed connection between ion binding and distal structural rearrangements, consensus triads from these phyla were installed in the myoc-OLF. All three protein variants exhibit wild-type-like or better stability, but their calcium-binding properties differ, concomitant with new structural deviations from wild-type myoc-OLF. Taken together, the results indicate that calcium binding is not intrinsically destabilizing to myoc-OLF or required to observe a well ordered side helix, and that ion binding is a differential feature that may underlie the largely elusive biological function of OLF propellers.

PubMed: 31478904
DOI: 10.1107/S205979831901074X

実験手法

X-RAY DIFFRACTION (1.9 Å)