Unexpected plasticity of the quaternary structure of iron-manganese superoxide dismutases

Autor(es)

Rengifo, Emerita Mendoza ; Fontolan, Laureana Stelmastchuk Benassi ; Ferreira-junior, Jose Ribamar ; Bleicher, Lucas ; Penner-Hahn, James ; Garratt, Richard Charles

• Tipo de documento: Artigo Científico
• Fonte: Journal of Structural Biology; v. 214, n. 2, p. 11-pg., 2022-04-11.

Resumo

Protein 3D structure can be remarkably robust to the accumulation of mutations during evolution. On the other hand, sometimes a single amino acid substitution can be sufficient to generate dramatic and completely unpredictable structural consequences. In an attempt to rationally alter the preferences for the metal ion at the active site of a member of the Iron/Manganese superoxide dismutase family, two examples of the latter phenomenon were identified. Site directed mutants of SOD from Trichoderma reesei were generated and studied crystallographically together with the wild type enzyme. Despite being chosen for their potential impact on the redox potential of the metal, two of the mutations (D150G and G73A) in fact resulted in significant alterations to the protein quaternary structure. The D150G mutant presented alternative inter-subunit contacts leading to a loss of symmetry of the wild type tetramer, whereas the G73A mutation transformed the tetramer into an octamer despite not participating directly in any of the inter-subunit interfaces. We conclude that there is considerable intrinsic plasticity in the Fe/MnSOD fold that can be unpredictably affected by single amino acid substitutions. In much the same way as phenotypic defects at the organism level can reveal much about normal function, so too can such mutations teach us much about the subtleties of protein structure. (AU)

• Processo FAPESP: 14/01855-2 - Explorando a seletividade por íons metálicos no sítio ativo da enzima Superóxido Dismutase (SOD) usando mutagênese sítio dirigida
• Beneficiário: Emérita Mendoza Rengifo
• Modalidade de apoio: Bolsas no Brasil - Mestrado