The interaction of CRM1 and the nuclear pore protein Tpr.
While much has been devoted to the study of transport mechanisms through the nuclear pore complex (NPC), the specifics of interactions and binding between export transport receptors and the NPC periphery have remained elusive. Recent work has demonstrated a binding interaction between the exportin CRM1 and the unstructured carboxylic tail of Tpr, on the nuclear basket. Strong evidence suggests that this interaction is vital to the functions of CRM1. Using molecular dynamics simulations and a newly refined method for determining binding regions, we have identified nine candidate binding sites on CRM1 for C-Tpr. These include two adjacent to RanGTP--from which one is blocked in the absence of RanGTP--and three next to the binding region of the cargo Snurportin. We report two additional interaction sites between C-Tpr and Snurportin, suggesting a possible role for Tpr import into the nucleus. Using bioinformatics tools we have conducted conservation analysis and functional residue prediction investigations to identify which parts of the obtained binding sites are inherently more important and should be highlighted. Also, a novel measure based on the ratio of available solvent accessible surface (RASAS) is proposed for monitoring the ligand/receptor binding process.
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
Charles L
CL
Zhao
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
Seyed Hanif
SH
Mahboobi
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
Ruhollah
R
Moussavi-Baygi
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California, United States of America.
Mohammad R K
MR
Mofrad
D001665:Binding Sites; D006801:Humans; D028884:Karyopherins / Q000737:chemistry; D008024:Ligands; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D022022:Nuclear Pore / Q000737:chemistry / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D039381:RNA Cap-Binding Proteins / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D012984:Software; D020931:ran GTP-Binding Protein / Q000737:chemistry; D000097606:Exportin 1 Protein
D028884:Karyopherins; D008024:Ligands; D028861:Nuclear Pore Complex Proteins; D011518:Proto-Oncogene Proteins; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C114090:SNUPN protein, human; C073597:TPR protein, human