5VR2

mouse myocilin leucine zipper C-terminal 7 heptad repeat

5VR2 の概要

• エントリーDOI: 10.2210/pdb5vr2/pdb
• 分子名称: Myocilin (2 entities in total)
• 機能のキーワード: coiled coil, disulfide bond, extracellular matrix, trabecular meshwork, leucine zipper, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Secreted . Myocilin, C-terminal fragment: Secreted . Myocilin, N-terminal fragment: Endoplasmic reticulum: O70624
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 23834.03

構造登録者

Lieberman, R.L.,Hill, S.E. (登録日: 2017-05-10, 公開日: 2017-11-08, 最終更新日: 2024-10-23)

主引用文献

Hill, S.E.,Nguyen, E.,Donegan, R.K.,Patterson-Orazem, A.C.,Hazel, A.,Gumbart, J.C.,Lieberman, R.L.
Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin.
Structure, 25:1697-1707.e5, 2017

PubMed Abstract: Glaucoma-associated myocilin is a member of the olfactomedins, a protein family involved in neuronal development and human diseases. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a Y-shaped parallel dimer-of-dimers with distinct tetramer and dimer regions. The structure of the dimeric C-terminal 7-heptad repeats elucidates an unexpected repeat pattern involving inter-strand stabilization by oppositely charged residues. Molecular dynamics simulations reveal an alternate accessible conformation in which the terminal inter-strand disulfide limits the extent of unfolding and results in a kinked configuration. By inference, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of naturally occurring extracellular coiled coils and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.

PubMed: 29056483
DOI: 10.1016/j.str.2017.09.008

実験手法

X-RAY DIFFRACTION (1.922 Å)