6B9F

Human ATL1 mutant - F151S bound to GDPAlF4-

6B9F の概要

• エントリーDOI: 10.2210/pdb6b9f/pdb
• 分子名称: Atlastin-1, GLYCEROL, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: gtpase, dynamin related protein, hsp mutant, hydrolysis-deficient, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Multi-pass membrane protein : Q8WXF7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 106760.28

構造登録者

O'Donnell, J.P.,Sondermann, H. (登録日: 2017-10-10, 公開日: 2017-12-06, 最終更新日: 2023-10-04)

主引用文献

O'Donnell, J.P.,Byrnes, L.J.,Cooley, R.B.,Sondermann, H.
A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.
J. Biol. Chem., 293:687-700, 2018

PubMed Abstract: The dynamin-related GTPase atlastin (ATL) catalyzes membrane fusion of the endoplasmic reticulum and thus establishes a network of branched membrane tubules. When ATL function is compromised, the morphology of the endoplasmic reticulum deteriorates, and these defects can result in neurological disorders such as hereditary spastic paraplegia and hereditary sensory neuropathy. ATLs harness the energy of GTP hydrolysis to initiate a series of conformational changes that enable homodimerization and subsequent membrane fusion. Disease-associated amino acid substitutions cluster in regions adjacent to ATL's catalytic site, but the consequences for the GTPase's molecular mechanism are often poorly understood. Here, we elucidate structural and functional defects of an atypical hereditary spastic paraplegia mutant, ATL1-F151S, that is impaired in its nucleotide-hydrolysis cycle but can still adopt a high-affinity homodimer when bound to a transition-state analog. Crystal structures of mutant proteins yielded models of the monomeric pre- and post-hydrolysis states of ATL. Together, these findings define a mechanism for allosteric coupling in which Phe is the central residue in a hydrophobic interaction network connecting the active site to an interdomain interface responsible for nucleotide loading.

PubMed: 29180453
DOI: 10.1074/jbc.RA117.000380

実験手法

X-RAY DIFFRACTION (1.9 Å)