6JLB

Crystal structure of lamin A/C fragment and assembly mechanisms of intermediate filaments

Summary for 6JLB

• Entry DOI: 10.2210/pdb6jlb/pdb
• Descriptor: Lamin A/C (1 entity in total)
• Functional Keywords: nuclear lamin, coiled-coil structure, intermediate filaments, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 140222.52

Authors

Ahn, J.,Jo, I.,Ha, N.C. (deposition date: 2019-03-04, release date: 2019-09-11, Last modification date: 2024-10-23)

Primary citation

Ahn, J.,Jo, I.,Kang, S.M.,Hong, S.,Kim, S.,Jeong, S.,Kim, Y.H.,Park, B.J.,Ha, N.C.
Structural basis for lamin assembly at the molecular level.
Nat Commun, 10:3757-3757, 2019

PubMed Abstract: Nuclear structure and function are governed by lamins, which are intermediate filaments that mostly consist of α-helices. Different lamin assembly models have been proposed based on low resolution and fragmented structures. However, their assembly mechanisms are still poorly understood at the molecular level. Here, we present the crystal structure of a long human lamin fragment at 3.2 Å resolution that allows the visualization of the features of the full-length protein. The structure shows an anti-parallel arrangement of the two coiled-coil dimers, which is important for the assembly process. We further discover an interaction between the lamin dimers by using chemical cross-linking and mass spectrometry analysis. Based on these two interactions, we propose a molecular mechanism for lamin assembly that is in agreement with a recent model representing the native state and could explain pathological mutations. Our findings also provide the molecular basis for assembly mechanisms of other intermediate filaments.

PubMed: 31434876
DOI: 10.1038/s41467-019-11684-x

Experimental method

X-RAY DIFFRACTION (3.205 Å)