Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations

Nguyen G, Sutinen A, Raasakka A, Muruganandam G, Loris R, Kursula P, Frontiers in Molecular Biosciences 7 (2021) DOI

SASDJ39 – Monomeric human ganglioside-induced differentiation-associated protein 1-like 1, GDAP1L1

Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform)
MWexperimental 44 kDa
MWexpected 44 kDa
VPorod 73 nm3
log I(s) 5.36×10-2 5.36×10-3 5.36×10-4 5.36×10-5
Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) small angle scattering data  s, nm-1
ln I(s)
Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) Guinier plot ln 5.36×10-2 Rg: 2.7 nm 0 (2.7 nm)-2 s2
(sRg)2I(s)/I(0)
Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) Kratky plot 1.104 0 3 sRg
p(r)
Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) pair distance distribution function Rg: 2.8 nm 0 Dmax: 10.0 nm

Data validation


Fits and models


log I(s)
 s, nm-1
Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) CORAL model

Synchrotron SAXS data from solutions of monomeric human GDAP1L1 in 20 mM TRIS pH 7.5, 150 mM NaCl, 1 mM TCEP, were collected on the B21 beam line at the Diamond Light Source (Didcot, UK) using a Pilatus 2M detector at a sample-detector distance of 3.9 m and at a wavelength of λ = 0.094 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography (SEC) SAS was employed. The SEC parameters were as follows: A 45.00 μl sample at 10 mg/ml was injected at a 0.07 ml/min flow rate onto a GE Superdex 200 Increase 3.2/300 column at 12°C. 620 successive 3 second frames were collected through the SEC elution profile. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted from the sample elution peak frames to generate the final SAXS profile.

Human GDAP1L1 is a paralogue of human GDAP1 sharing 55% sequence identity. The atomistic representation of human GDAP1L1 shown above was modelled to the SAXS data with CORAL using the GDAP1 variant as an input structure (Protein Data Bank, PDB, 7AIA and refer to UniProt entry Q8TB36).

Ganglioside-induced differentiation-associated protein 1-like 1 (∆125-143 isoform) (GDAP1L1)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Monomer
Mon. MW   43.8 kDa
 
UniProt   Q96MZ0
Sequence   FASTA