Interesting structural and dynamical behaviors exhibited by the AF-6 PDZ domain upon Bcr peptide binding.
PDZ (postsynaptic density-95, disks large, zonula occludens-1) domains are small, protein-protein interaction modules that have multiple binding surfaces for the docking of diverse molecules. These domains can propagate signals from ligand-binding site to distal regions of the structure through allosteric communication. Recent works have revealed that picosecond to nanosecond time scale dynamics play a potential role in propagating long-range signals within a protein. Comparison of AF-6 PDZ domain structures in free and complex forms shows a conformation rearrangement of distal surface 2, which is far from the peptide binding groove. The relaxation dispersion experiments detected that the free AF-6 PDZ domain was sampling multiple conformations; millisecond dynamics mapped a network for allostery signal transmission throughout the AF-6 PDZ domain in the weak saturation state, and intramolecular motions were observed in distal surface 1 when the protein was saturated. These results provide evidence that the allosteric process in the AF-6 PDZ domain is not two-state; instead, the millisecond dynamic network provides a mechanism for the transmission of allosteric signals throughout a protein. Interestingly, the two distal surfaces of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1 changes in millisecond dynamics, whereas distal surface 2 undergoes structural rearrangement. The significance of the different response patterns in the signaling pathway and its relevance to the function of the AF-6 PDZ domain should be studied further.
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, and School of Life Sciences, Hefei, Anhui 230026, People's Republic of China.
Xiaogang
X
Niu
Quan
Q
Chen
Jiahai
J
Zhang
Weiqun
W
Shen
Yunyu
Y
Shi
Jihui
J
Wu
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D054731:PDZ Domains; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D051562:Proto-Oncogene Proteins c-bcr / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
C095516:AFDN protein, human; D010446:Peptide Fragments; D051562:Proto-Oncogene Proteins c-bcr; D009218:Myosins; D016547:Kinesins