7UUW

Cryogenic electron microscopy 3D map of F-actin bound by the Actin Binding Domain of alpha-catenin ortholog, HMP1

Summary for 7UUW

• Entry DOI: 10.2210/pdb7uuw/pdb
• EMDB information: 26748 26805
• Descriptor: Actin, alpha skeletal muscle, Alpha-catenin-like protein hmp-1, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: alpha-catenin, hmp1, actin binding domain, f-actin, f-actin binding protein, cell-cell junction, cell adhesion
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 12
• Total formula weight: 426698.17

Authors

Rangarajan, E.S.,Smith, E.W.,Izard, T. (deposition date: 2022-04-29, release date: 2023-01-18, Last modification date: 2023-01-25)

Primary citation

Rangarajan, E.S.,Smith, E.W.,Izard, T.
The nematode alpha-catenin ortholog, HMP1, has an extended alpha-helix when bound to actin filaments.
J.Biol.Chem., 299:102817-102817, 2022

PubMed Abstract: The regulation of cell-cell junctions during epidermal morphogenesis ensures tissue integrity, a process regulated by α-catenin. This cytoskeletal protein connects the cadherin complex to filamentous actin at cell-cell junctions. The cadherin-catenin complex plays key roles in cell physiology, organism development, and disease. While mutagenesis of Caenorhabditis elegans cadherin and catenin shows that these proteins are key for embryonic morphogenesis, we know surprisingly little about their structure and attachment to the cytoskeleton. In contrast to mammalian α-catenin that functions as a dimer or monomer, the α-catenin ortholog from C. elegans, HMP1 for humpback, is a monomer. Our cryogenic electron microscopy (cryoEM) structure of HMP1/α-catenin reveals that the amino- and carboxy-terminal domains of HMP1/α-catenin are disordered and not in contact with the remaining HMP1/α-catenin middle domain. Since the carboxy-terminal HMP1/α-catenin domain is the F-actin-binding domain (FABD), this interdomain constellation suggests that HMP1/α-catenin is constitutively active, which we confirm biochemically. Our perhaps most surprising finding, given the high sequence similarity between the mammalian and nematode proteins, is our cryoEM structure of HMP1/α-catenin bound to F-actin. Unlike the structure of mammalian α-catenin bound to F-actin, binding to F-actin seems to allosterically convert a loop region of the HMP1/α-catenin FABD to extend an HMP1/α-catenin FABD α-helix. We use cryoEM and bundling assays to show for the first time how the FABD of HMP1/α-catenin bundles actin in the absence of force. Collectively, our data advance our understanding of α-catenin regulation of cell-cell contacts and additionally aid our understanding of the evolution of multicellularity in metazoans.

PubMed: 36539037
DOI: 10.1016/j.jbc.2022.102817

Experimental method

ELECTRON MICROSCOPY (3.36 Å)