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:31402219
Additional 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

No weblogo for data of varying length.
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
1GK4 2001-08-08T00:00:00+0000 2.3 HUMAN VIMENTIN COIL 2B FRAGMENT (CYS2)
1GK6 2001-08-08T00:00:00+0000 1.9 Human vimentin coil 2B fragment linked to GCN4 leucine zipper (Z2B)
1GK7 2001-08-08T00:00:00+0000 1.4 HUMAN VIMENTIN COIL 1A FRAGMENT (1A)
3G1E 2009-01-29T00:00:00+0000 1.83 X-ray crystal structure of coil 1A of human vimentin
3KLT 2009-11-09T00:00:00+0000 2.7 Crystal structure of a vimentin fragment
3S4R 2011-05-20T00:00:00+0000 2.45 Crystal structure of vimentin coil1A/1B fragment with a stabilizing mutation
3SSU 2011-07-08T00:00:00+0000 2.6 Crystal structure of vimentin coil1A/1B fragment
3SWK 2011-07-14T00:00:00+0000 1.7 Crystal structure of vimentin coil1B fragment
3TRT 2011-09-10T00:00:00+0000 2.3 Crystal structure of stabilised vimentin coil2 fragment
3UF1 2011-10-31T00:00:00+0000 2.81 Crystal Structure of Vimentin (fragment 144-251) from Homo sapiens, Northeast Structural Genomics Consortium Target HR4796B

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Human Vimentin P08670 VIME_HUMAN
93.8 Human Vimentin P48616 VIME_BOVIN
98.7 Human Vimentin P84198 VIME_CHLAE
98.7 Human Vimentin Q4R4X4 VIME_MACFA
98.7 Human Vimentin Q5R1W8 VIME_PANTR
97.2 Human Vimentin P02543 VIME_PIG
93.6 Human Vimentin P31000 VIME_RAT
93.6 Human Vimentin P20152 VIME_MOUSE
93.3 Human Vimentin P02544 VIME_MESAU
93.2 Human Vimentin P48670 VIME_CRIGR