PDBsum entry 4z8g

Protein binding

PDB id: 4z8g

Contents

Protein chain

175 a.a.

Metals

_NI ×9

Waters ×113

PDB id:

4z8g

Name:

Protein binding

Title:

Chimera of tropomodulin-1 and leiomodin-1 actin-binding site 2 (tl1 abs2)

Structure:

Tropomodulin-1, leiomodin-1 chimera (tp1 abs2). Chain: a. Fragment: tropomodulin-1 residues 163-228 (unp), leiomodin-1 actin- binding site 2 (unp residues 364-486). Synonym: tl1, erythrocyte tropomodulin, e-tmod,64 kda autoantigen 1d, 64 kda autoantigen 1d3, 64 kda autoantigen d1, leiomodin, muscle form, smooth muscle leiomodin, sm-lmod, thyroid-associated ophthalmopathy autoantigen. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tmod1, d9s57e, tmod, lmod1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.194 R-free: 0.254

Authors:

M.Boczkowska,G.Rebowski,R.Dominguez

Key ref:

M.Boczkowska et al. (2015). How Leiomodin and Tropomodulin use a common fold for different actin assembly functions. Nat Commun, 6, 8314. PubMed id: 26370058 DOI: 10.1038/ncomms9314

Date:

08-Apr-15 Release date: 21-Oct-15

Protein chain

P28289  (TMOD1_HUMAN) -  Tropomodulin-1 from Homo sapiens

Seq: 359 a.a.

Struc: 175 a.a.*

Protein chain

P29536  (LMOD1_HUMAN) -  Leiomodin-1 from Homo sapiens

Seq: 600 a.a.

Struc: 175 a.a.*

* PDB and UniProt seqs differ at 98 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/ncomms9314

Nat Commun 6:8314 (2015)

PubMed id: 26370058

How Leiomodin and Tropomodulin use a common fold for different actin assembly functions.

M.Boczkowska, G.Rebowski, E.Kremneva, P.Lappalainen, R.Dominguez.

ABSTRACT

How proteins sharing a common fold have evolved different functions is a fundamental question in biology. Tropomodulins (Tmods) are prototypical actin filament pointed-end-capping proteins, whereas their homologues, Leiomodins (Lmods), are powerful filament nucleators. We show that Tmods and Lmods do not compete biochemically, and display similar but distinct localization in sarcomeres. Changes along the polypeptide chains of Tmods and Lmods exquisitely adapt their functions for capping versus nucleation. Tmods have alternating tropomyosin (TM)- and actin-binding sites (TMBS1, ABS1, TMBS2 and ABS2). Lmods additionally contain a C-terminal extension featuring an actin-binding WH2 domain. Unexpectedly, the different activities of Tmods and Lmods do not arise from the Lmod-specific extension. Instead, nucleation by Lmods depends on two major adaptations-the loss of pointed-end-capping elements present in Tmods and the specialization of the highly conserved ABS2 for recruitment of two or more actin subunits. The WH2 domain plays only an auxiliary role in nucleation.