9ZZK

One Lmod2 and incoming actin at the pointed end of F-actin

Summary for 9ZZK

• Entry DOI: 10.2210/pdb9zzk/pdb
• EMDB information: 75004
• Descriptor: Actin, alpha skeletal muscle, Leiomodin-2, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: actin, lmod2, leiomodin, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 316908.26

Authors

Brotzman, S.B.,Palmer, N.J.,Dominguez, R. (deposition date: 2026-01-07, release date: 2026-06-24, Last modification date: 2026-08-05)

Primary citation

Biswas, S.,Larrinaga, T.M.,Choubey, S.,Gregorio, C.C.,Shekhar, S.
Leiomodin 2 is a processive pointed-end elongator of actin filaments.
Nat Commun, 17:-, 2026

PubMed Abstract: The actin cytoskeleton drives essential processes like cell migration and muscle contraction. While barbed-end polymerization is well-established, pointed-end elongation was long considered impossible in vivo. Here, we demonstrate that Leiomodin 2 (Lmod2), which localizes to thin-filament pointed ends in striated muscle cells, functions as an actin polymerase for pointed-end elongation. Single-molecule and single-filament imaging reveal that Lmod2 remains processively bound to pointed ends in vitro, enabling elongation even in the presence of high profilin concentrations found in the cytoplasm that otherwise would cause depolymerization of free pointed ends. Kinetic analysis indicates that Lmod2-mediated elongation proceeds through a linked two-step mechanism, in which monomer addition is followed by a first-order transition at the Lmod2-bound pointed end that limits elongation at high actin concentrations. Lmod2's activity also persists in the presence of tropomyosin, underscoring its physiological relevance. Both processivity and elongation rate of Lmod2 are dependent on its WH2 domain. Remarkably, human dilated cardiomyopathy-associated mutations in Lmod2 greatly reduce Lmod2's pointed-end elongation activity, providing a potential mechanism for disease progression and supporting a role for Lmod2-mediated polymerization in the formation and maintenance of muscle sarcomeres.

PubMed: 42477321
DOI: 10.1038/s41467-026-74809-z

Experimental method

ELECTRON MICROSCOPY (4.06 Å)