Ligation-Dependent Picosecond Dynamics in Human Hemoglobin As Revealed by Quasielastic Neutron Scattering

Abstract

Hemoglobin, the vital O carrier in red blood cells, has long served as a classic example of an allosteric protein. Although high-resolution X-ray structural models are currently available for both the deoxy tense (T) and fully liganded relaxed (R) states of hemoglobin, much less is known about their dynamics, especially on the picosecond to subnanosecond time scales. Here, we investigate the picosecond dynamics of the deoxy and CO forms of human hemoglobin using quasielastic neutron scattering under near physiological conditions in order to extract the dynamics changes upon ligation. From the analysis of the global motions, we found that whereas the apparent diffusion coefficients of the deoxy form can be described by assuming translational and rotational diffusion of a rigid body, those of the CO form need to involve an additional contribution of internal large-scale motions. We also found that the local dynamics in the deoxy and CO forms are very similar in amplitude but are slightly lower in frequency in the former than in the latter. Our results reveal the presence of rapid large-scale motions in hemoglobin and further demonstrate that this internal mobility is governed allosterically by the ligation state of the heme group.

Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

“…4B-D) were approximately 1.2 (Fig. 4E), similar to other examples: ~1.2 (300-310 K) in human hemoglobin (Hb) 33 and ~1.2 (290-300 K) in α-synuclein (αSyn) 34 . Thus, KaiC WT and the KaiC mutants were maintained as intact hexamers during the QENS measurements, and underwent the same translational and rotational diffusions as ordinary proteins.…”

“…More detailed comparisons of internal motions are possible by making reference for QENS data for Hb 33 and αSyn 51 , which were acquired at the same beamline with the same energy resolution (12 μeV / 55 ps). As shown in Fig.…”

High-resolution neutron spectroscopy using backscattering and neutron spin-echo spectrometers in soft and hard condensed matter

“…Observed collective motions on the 100 ps timescale are pathways for the largerscale domain motions that are accessible with NSE 57 in protein solutions as indicated by results from molecular dynamics simulations, which are in good agreement with the experimental data. Another example of the study of the collective motions of proteins 58 in the sub-nanosecond timescale involved the careful analysis of QENS data from human deoxyhaemoglobin and CO-bound haemoglobin in solution, revealing that although the deoxyhaemoglobin performs simple translational and rotational rigid-body movements, the CObound form exhibits additional large-scale motions that result from the ligation state of the heme group.…”

Quartz Cell for a Backscattering Spectrometer

“…The QC is available for use. A report on using this QC for a protein solution system has already been published [9], and the details of the QC were also described.…”