INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Molecular basis of the thermal stability in truncated (2/2) hemoglobins
J.P. BUSTAMANTE; A. BONAMORE; A.D. NADRA; SCIAMANNA, N.; BOFFI, A.; D. A. ESTRIN; L. BOECHI
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
ELSEVIER SCIENCE BV
Lugar: Amsterdam; Año: 2014 vol. 1840 p. 2281 - 2281
Background: Understanding the molecular mechanism through which proteins are functional at extreme highand low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we havefocused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuber-culosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at hightemperatures.Methods: We used molecular dynamics simulations at different temperatures as well as thermal melting profilemeasurements of both wild type proteins and two mutants designed to interchange the amino acid residue, eitherPro or Gly, at E3 position.Results: The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°)the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structureof the CD loop, making it more flexible.Conclusions: This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoidunfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions,together augmenting the protein´s thermostability.General significance: These results indicate a clear structural and dynamical role of a key residue for thermalstability in truncated hemoglobins.