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EXPLORE NORTHEASTERN

James Manning

Professor

Mailing Address:

134 MU (Mugar Life Sciences Building), Boston, MA 02115

Expertise:

  • Protein Structure and Function

Our goal is to further our understanding of proteins, especially those that have important biological functions. We employ both the classical methods of protein chemistry as well as the newer recombinant DNA technology.

Hemoglobin – A previously unrecognized function of normal human hemoglobins occurring during protein assembly is self-regulation of subunit pairings and their durations arising from the variable strengths of their subunit interactions. The subunit interface strengths of the normal embryonic, fetal, and adult human hemoglobins have not been considered to differ significantly. However, we found that the strengths, i.e., the free energies of the tetramer – dimer interfaces, contrary to previous reports, differ by 3 orders of magnitude and display an undulating profile similar to the transitions (“switches”) of various globin subunit types over time. The dimer interface strengths are also variable and correlate linearly with their developmental profile. Embryonic hemoglobins are the weakest; fetal hemoglobin is of intermediate strength, and adult hemoglobins are the strongest. The relative contributions of globin gene order and competition among subunits due to differences in their interface strengths were found to be complementary and establish a connection for genetics, thermodynamics, and development.

Protein Acetylation – This widespread post-translational modification is poorly understood. Several years ago, we found that the N-terminal acetylation of fetal hemoglobin significantly weakens its subunit interactions. We have recently studied acetylation of lysines in histones which is involved in gene activation; serine phosphorylation is also linked to this process. Two new publications focus on peptides comprising histone sequences with various acetylation/phosphorylation patterns in order to decipher how their interrelationship influences gene expression.