TY - JOUR
T1 - Order from disorder in the sarcomere
T2 - FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin
AU - Sponga, Antonio
AU - Arolas, Joan L.
AU - Schwarz, Thomas C.
AU - Jeffries, Cy M.
AU - Chamorro, Ariadna Rodriguez
AU - Kostan, Julius
AU - Ghisleni, Andrea
AU - Drepper, Friedel
AU - Polyansky, Anton
AU - de Almeida Ribeiro, Euripedes
AU - Pedron, Miriam
AU - Zawadzka-Kazimierczuk, Anna
AU - Mlynek, Georg
AU - Peterbauer, Thomas
AU - Doto, Pierantonio
AU - Schreiner, Claudia
AU - Hollerl, Eneda
AU - Mateos, Borja
AU - Geist, Leonhard
AU - Faulkner, Georgine
AU - Kozminski, Wiktor
AU - Svergun, Dmitri I.
AU - Warscheid, Bettina
AU - Zagrovic, Bojan
AU - Gautel, Mathias
AU - Konrat, Robert
AU - Djinović-Carugo, Kristina
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2021/5/28
Y1 - 2021/5/28
N2 - In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with α-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.
AB - In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with α-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.
KW - PROTEIN SECONDARY STRUCTURE
KW - PARAMAGNETIC RELAXATION ENHANCEMENT
KW - BACKBONE RESONANCE ASSIGNMENT
KW - SMALL-ANGLE SCATTERING
KW - Z-DISC
KW - STRUCTURAL-CHARACTERIZATION
KW - INTRINSIC DISORDER
KW - FOURIER-TRANSFORM
KW - UNFOLDED PROTEINS
KW - FILAMIN-BINDING
UR - http://www.scopus.com/inward/record.url?scp=85106995198&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abg7653
DO - 10.1126/sciadv.abg7653
M3 - Article
C2 - 34049882
AN - SCOPUS:85106995198
VL - 7
JO - Science Advances
JF - Science Advances
SN - 2375-2548
IS - 22
M1 - eabg7653
ER -