7dtg
Crystal structure of lamin B1 Ig-like domain from human
Structural highlights
DiseaseLMNB1_HUMAN Defects in LMNB1 are the cause of leukodystrophy demyelinating autosomal dominant adult-onset (ADLD) [MIM:169500. ADLD is a slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis.[1] FunctionLMNB1_HUMAN Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Publication Abstract from PubMedLamins are nuclear intermediate filament proteins that play an essential role in maintaining the nuclear structure by forming a 3-D meshwork. Lamins consist of the N-terminal unstructured head, the coiled-coil rod domain, and the C-terminal tail, which is mostly unstructured except for the Ig-like domain. To date, the Ig-like domain has been characterized as a monomeric structure. Here, we determined the crystal structures of human lamin A/C, including the Ig-like domain and its N- and C-terminal flanking sequences. Interestingly, the structures showed a homodimer formed by beta-strand interactions between the N- and C-terminal flanking sequences. This interaction also provides a molecular implication for the creation of a 3-D meshwork between the 3.5-nm-thick filaments. Furthermore, we determined the crystal structure of the corresponding region of lamin B1. The structure showed a similar dimeric assembly, also formed by beta-strand interactions, albeit the intersubunit distance was much shorter. Since the Ig-like domain contains many genetic hotspots causing lamin-related diseases in lamin A/C, our findings will help understand the detailed assembly of lamins in a 3-D meshwork structure and lamin-related diseases at the molecular level. Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1.,Ahn J, Lee J, Jeong S, Kang SM, Park BJ, Ha NC Biochem Biophys Res Commun. 2021 Apr 23;550:191-196. doi:, 10.1016/j.bbrc.2021.02.102. Epub 2021 Mar 9. PMID:33706103[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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