Proteins with calmodulin-like domains: structures and functional roles

TY - JOUR

T1 - Proteins with calmodulin-like domains

T2 - structures and functional roles

AU - Villalobo, Antonio

AU - González-Muñoz, María

AU - Berchtold, Martin W.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - The appearance of modular proteins is a widespread phenomenon during the evolution of proteins. The combinatorial arrangement of different functional and/or structural domains within a single polypeptide chain yields a wide variety of activities and regulatory properties to the modular proteins. In this review, we will discuss proteins, that in addition to their catalytic, transport, structure, localization or adaptor functions, also have segments resembling the helix-loop-helix EF-hand motifs found in Ca 2+ -binding proteins, such as calmodulin (CaM). These segments are denoted CaM-like domains (CaM-LDs) and play a regulatory role, making these CaM-like proteins sensitive to Ca 2+ transients within the cell, and hence are able to transduce the Ca 2+ signal leading to specific cellular responses. Importantly, this arrangement allows to this group of proteins direct regulation independent of other Ca 2+ -sensitive sensor/transducer proteins, such as CaM. In addition, this review also covers CaM-binding proteins, in which their CaM-binding site (CBS), in the absence of CaM, is proposed to interact with other segments of the same protein denoted CaM-like binding site (CLBS). CLBS are important regulatory motifs, acting either by keeping these CaM-binding proteins inactive in the absence of CaM, enhancing the stability of protein complexes and/or facilitating their dimerization via CBS/CLBS interaction. The existence of proteins containing CaM-LDs or CLBSs substantially adds to the enormous versatility and complexity of Ca 2+ /CaM signaling.

AB - The appearance of modular proteins is a widespread phenomenon during the evolution of proteins. The combinatorial arrangement of different functional and/or structural domains within a single polypeptide chain yields a wide variety of activities and regulatory properties to the modular proteins. In this review, we will discuss proteins, that in addition to their catalytic, transport, structure, localization or adaptor functions, also have segments resembling the helix-loop-helix EF-hand motifs found in Ca 2+ -binding proteins, such as calmodulin (CaM). These segments are denoted CaM-like domains (CaM-LDs) and play a regulatory role, making these CaM-like proteins sensitive to Ca 2+ transients within the cell, and hence are able to transduce the Ca 2+ signal leading to specific cellular responses. Importantly, this arrangement allows to this group of proteins direct regulation independent of other Ca 2+ -sensitive sensor/transducer proteins, such as CaM. In addition, this review also covers CaM-binding proteins, in which their CaM-binding site (CBS), in the absence of CaM, is proposed to interact with other segments of the same protein denoted CaM-like binding site (CLBS). CLBS are important regulatory motifs, acting either by keeping these CaM-binding proteins inactive in the absence of CaM, enhancing the stability of protein complexes and/or facilitating their dimerization via CBS/CLBS interaction. The existence of proteins containing CaM-LDs or CLBSs substantially adds to the enormous versatility and complexity of Ca 2+ /CaM signaling.

KW - Calcineurin

KW - Calpain

KW - Epidermal growth factor receptor

KW - Glycerol-3-phosphate dehydrogenase

KW - Na /H exchanger

KW - NADPH oxidases

KW - Plasma membrane Ca -ATPase

KW - Protein kinases

KW - α-Actinin

U2 - 10.1007/s00018-019-03062-z

DO - 10.1007/s00018-019-03062-z

M3 - Review

C2 - 30877334

AN - SCOPUS:85062998221

SN - 1420-682X

VL - 76

SP - 2299

EP - 2328

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 12

ER -