Eye lens β-crystallins are predicted by native ion mobility-mass spectrometry and computations to form compact higher-ordered heterooligomers.

Autor:	Rolland AD; Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, OR 97403-1253, USA., Takata T; Kyoto University, Research Reactor Institute 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan., Donor MT; Department of Biological & Molecular Sciences, George Fox University, 414 N Meridian St, Newberg, OR 97132, USA., Lampi KJ; Integrative Biosciences, School of Dentistry, 3181 SW Sam Jackson Park Road, Oregon Health & Science University, Portland, OR 97239-3098, USA. Electronic address: lampik@ohsu.edu., Prell JS; Department of Chemistry and Biochemistry, 1253 University of Oregon, Eugene, OR 97403-1253, USA; Materials Science Institute, 1252 University of Oregon, Eugene, OR 97403-1252, USA. Electronic address: jprell@uoregon.edu.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2023 Sep 07; Vol. 31 (9), pp. 1052-1064.e3. Date of Electronic Publication: 2023 Jul 14.
DOI:	10.1016/j.str.2023.06.013
Abstrakt:	Eye lens α- and β-/γ-crystallin proteins are not replaced after fiber cell denucleation and maintain lens transparency and refractive properties. The exceptionally high (∼400-500 mg/mL) concentration of crystallins in mature lens tissue and multiple other factors impede precise characterization of β-crystallin interactions, oligomer composition, size, and topology. Native ion mobility-mass spectrometry is used here to probe β-crystallin association and provide insight into homo- and heterooligomerization kinetics for these proteins. These experiments include separation and characterization of higher-order β-crystallin oligomers and illustrate the unique advantages of native IM-MS. Recombinantly expressed βB1, βB2, and βA3 isoforms are found to have different homodimerization propensities, and only βA3 forms larger homooligomers. Heterodimerization of βB2 with βA3 occurs ∼3 times as fast as that of βB1 with βA3, and βB1 and βB2 heterodimerize less readily. Ion mobility experiments, molecular dynamics simulations, and PISA analysis together reveal that observed oligomers are consistent with predominantly compact, ring-like topologies. Competing Interests: Declaration of interests The authors declare no competing financial interest. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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