Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations.
Abstract
Electron paramagnetic resonance (EPR) spectroscopy of full-length vimentin and X-ray crystallography of vimentin peptides has provided concordant structural data for nearly the entire central rod domain of the protein. In this report, we use a combination of EPR spectroscopy and molecular modeling to determine the structure and dynamics of the missing region and unite the separate elements into a single structure. Validation of the linker 1-2 (L1-2) modeling approach is demonstrated by the close correlation between EPR and X-ray data in the previously solved regions. Importantly, molecular dynamic (MD) simulation of the constructed model agrees with spin label motion as determined by EPR. Furthermore, MD simulation shows L1-2 heterogeneity, with a concerted switching of states among the dimer chains. These data provide the first ever experimentally driven model of a complete intermediate filament rod domain, providing research tools for further modeling and assembly studies.
Submission Details
ID: Jd8BmmXZ
Submitter: David Gae
Submission Date: June 12, 2020, 11:14 a.m.
Version: 1
Publication Details
Hess JF, Budamagunta MS, Gae DD, McCarrick RM, Lorigan GA, Voss JC, FitzGerald PG,Structure (2019) Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations. PMID:31402219Additional Information
Sequence of the structural domain covered in this paper. (Rod1B-L12-Rod2) GQGKSRLGDLYEEEMRELRRQVDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQELQAQIQEQHVQIDVDVSKPDLTAALRDVRQQYESVAAKNLQEAEEWYKSKFADLSEAANRNNDALRQAKQESTEYRRQVQSLTCEVDALK
Study Summary
| Number of data points | 3 |
| Proteins | Human Vimentin |
| Unique complexes | 3 |
| Assays/Quantities/Protocols | Experimental Assay: Electron Microscope |
| Libraries | Electron microscope of vimentin protofilament data |
| Supplemental data | Final restrained structure ; Vimentin complete EPR xray data |
Structure view and single mutant data analysis
Study data
| Colors: | D | E | R | H | K | S | T | N | Q | A | V | I | L | M | F | Y | W | C | G | P |
|---|
Data Distribution
Studies with similar sequences (approximate matches)
Correlation with other assays (exact sequence matches)
Relevant PDB Entries
| Structure ID | Release Date | Resolution | Structure Title |
|---|---|---|---|
| 4YPC | 2015-03-12T00:00:00+0000 | 1.44 | Trimeric crystal structure of vimentin coil1B fragment |
| 4MCY | 2013-08-22T00:00:00+0000 | 2.3 | Immune Receptor |
| 1GK6 | 2001-08-08T00:00:00+0000 | 1.9 | Human vimentin coil 2B fragment linked to GCN4 leucine zipper (Z2B) |
| 6ATI | 2017-08-29T00:00:00+0000 | 1.98 | HLA-DRB1*1402 in complex with Vimentin-64Cit59-71 |
| 3SWK | 2011-07-14T00:00:00+0000 | 1.7 | Crystal structure of vimentin coil1B fragment |
| 4MD0 | 2013-08-22T00:00:00+0000 | 2.19 | Immune Receptor |
| 4MD5 | 2013-08-22T00:00:00+0000 | 1.65 | Immune Receptor |
| 6ATF | 2017-08-29T00:00:00+0000 | 1.9 | HLA-DRB1*1402 in complex with Vimentin59-71 |
| 1GK4 | 2001-08-08T00:00:00+0000 | 2.3 | HUMAN VIMENTIN COIL 2B FRAGMENT (CYS2) |
| 4MCZ | 2013-08-22T00:00:00+0000 | 2.41 | Immune Receptor |
Relevant UniProtKB Entries
| Percent Identity | Matching Chains | Protein | Accession | Entry Name |
|---|---|---|---|---|
| 93.2 | Human Vimentin | P48670 | VIME_CRIGR | |
| 93.3 | Human Vimentin | P02544 | VIME_MESAU | |
| 93.6 | Human Vimentin | P20152 | VIME_MOUSE | |
| 93.6 | Human Vimentin | P31000 | VIME_RAT | |
| 97.2 | Human Vimentin | P02543 | VIME_PIG | |
| 98.7 | Human Vimentin | Q5R1W8 | VIME_PANTR | |
| 98.7 | Human Vimentin | Q4R4X4 | VIME_MACFA | |
| 98.7 | Human Vimentin | P84198 | VIME_CHLAE | |
| 93.8 | Human Vimentin | P48616 | VIME_BOVIN | |
| 100.0 | Human Vimentin | P08670 | VIME_HUMAN |