Picosecond Protein Movements

Protein structure can be studied by crystallography or spectroscopy, which can also probe movement. Mukherjee and colleagues used 2 dimensional infrared spectroscopy (2D IR) to study the motions of a peptide on the scale of picoseconds, or trillionths of a second. (Interactions between proteins occur about a million times slower, on the mico- to millisecond time scales probed by NMR.) The 27 amino acid peptide that they studied spans the transmembrane region of CD3zeta, a signaling subunit of T lymphocyte antigen receptor. The peptide forms an alpha helix within the membrane. They synthesized 11 peptides, each with an amide [13]C labeled at a different position. Using a vibrational echo pulse sequence to resolve fast and slow molecular dynamics, they varied the delay between the pulses to measure motion on the picosecond scale. This revealed that all amino acids along the peptide showed the same relaxation times, which were similar to those observed in other peptides in solution, suggesting that this behavior is intrinsic to peptides. Comparisons with a molecular dynamic simulation confirmed that the peptides formed tetramers. They also found 2 'kinks' in the alpha helix, causing a 'funnel' structure to form in the membrane. Based on their observations of how the polar water molecules and lipid headgroups interact with the labeled amides, they predict that the IR patterns of amino acids lining the pores of transmembrane channel proteins will be easily distinguished from those facing the membrane.
Mukherjee P, Kass I, Arkin I, Zanni MT. "Picosecond dynamics of a membrane protein revealed by 2D IR." Proc. Natl. Acad. Sci. U S A. 2006 Feb 27;