PDBsum entry 6b9e

Hydrolase

PDB id: 6b9e

Contents

Protein chains

392 a.a.

Ligands

GDP ×2

SO4

Metals

_MG ×2

Waters ×198

PDB id:

6b9e

Name:

Hydrolase

Title:

Human atl1 mutant - r77a / f151s bound to gdp

Structure:

Atlastin-1. Chain: a, b. Fragment: residues 1-446. Synonym: brain-specific gtp-binding protein,gtp-binding protein 3, hgbp3,guanine nucleotide-binding protein 3,spastic paraplegia 3 protein a. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: atl1, gbp3, spg3a. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.99Å R-factor: 0.204 R-free: 0.244

Authors:

J.P.O'Donnell,H.Sondermann

Key ref:

J.P.O'Donnell et al. (2018). A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core. J Biol Chem, 293, 687-700. PubMed id: 29180453

Date:

10-Oct-17 Release date: 06-Dec-17

Protein chains

Q8WXF7  (ATLA1_HUMAN) -  Atlastin-1 from Homo sapiens

Seq: 558 a.a.

Struc: 392 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.6.5.- - ?????

J Biol Chem 293:687-700 (2018)

PubMed id: 29180453

A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.

J.P.O'Donnell, L.J.Byrnes, R.B.Cooley, H.Sondermann.

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 Phe¹⁵¹is the central residue in a hydrophobic interaction network connecting the active site to an interdomain interface responsible for nucleotide loading.