Nanoparticle Assisted Remodeling of Proteotoxic SOD1 Mutants Alters the Biointerface of the Functional Interaction of Microtubules and Kinesin Motors

Kyongwan Kim; Selvaraj Subramaniyam; Ahmad Galaleldeen; Hikaru Nakazawa; Mitsuo Umetsu; Winfried Teizer; Sanjib Bhattacharyya

doi:10.1021/acsabm.9b00501

Nanoparticle Assisted Remodeling of Proteotoxic SOD1 Mutants Alters the Biointerface of the Functional Interaction of Microtubules and Kinesin Motors

ACS Appl Bio Mater. 2019 Oct 21;2(10):4121-4128. doi: 10.1021/acsabm.9b00501. Epub 2019 Oct 4.

Authors

Kyongwan Kim, Selvaraj Subramaniyam¹, Ahmad Galaleldeen², Hikaru Nakazawa, Mitsuo Umetsu, Winfried Teizer, Sanjib Bhattacharyya¹

Affiliations

¹ Department of Pharmaceutical Science and Chinese Traditional Medicine, Southwest University, Beibei, Chongqing 400715, China.
² Department of Biological Science, St Mary's University, San Antonio, Texas 78228, United States.

PMID: 35021426
DOI: 10.1021/acsabm.9b00501

Abstract

Transport deficits with motor neuron degeneration have been implicated in amyotrophic lateral sclerosis (ALS). We report a biomimetic system composed of microtubules/kinesin motor that mimics the dysregulated motor dynamics of ALS. Pathogenic ALS mutants A4V SOD1 completely shut off motility. Treatment with 5 nm citrate coated gold nanoparticles recovers the impaired motor stepping by remodeling the A4V SOD1 rather than stabilizing microtubules or protein folding. Instead, gold nanoparticles alter the protein by a mechanism that reforms protein elements of A4V SOD1, in turn fixing the aberrant interaction of kinesin with microtubules. Reinstating kinesin motility holds potential for managing debilitating ALS.

Keywords: Biomimicking transport; Proteotoxicity; gold nanopaticles; microtubule self-assembly; motor restorations; mutant superoxide dismutase 1 (SOD1); quantum dot kinesin.