7BF1

Ca2+-Calmodulin in complex with peptide from brain-type creatine kinase in extended 1:2 binding mode

This is a non-PDB format compatible entry.

Summary for 7BF1

• Entry DOI: 10.2210/pdb7bf1/pdb
• Descriptor: Calmodulin-1, Creatine kinase B-type, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: calmodulin, calmodulin-peptide complex, creatine kinase, calcium signaling, energy metabolism, cytosolic protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 21460.14

Authors

Sprenger, J.,Akerfeldt, K.S.,Bredfelt, J.,Patel, N.,Rowlett, R.,Trifan, A.,Vanderbeck, A.,Lo Leggio, L.,Snogerup Linse, S. (deposition date: 2020-12-31, release date: 2021-07-21, Last modification date: 2024-01-31)

Primary citation

Sprenger, J.,Trifan, A.,Patel, N.,Vanderbeck, A.,Bredfelt, J.,Tajkhorshid, E.,Rowlett, R.,Lo Leggio, L.,Akerfeldt, K.S.,Linse, S.
Calmodulin complexes with brain and muscle creatine kinase peptides.
Curr Res Struct Biol, 3:121-132, 2021

PubMed Abstract: Calmodulin (CaM) is a ubiquitous Ca sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. This study reports two high-resolution X-ray structures, determined to 1.24 ​Å and 1.43 ​Å resolution, of calmodulin in complex with peptides from human brain and muscle CK, respectively. Both complexes adopt a rare extended binding mode with an observed stoichiometry of 1:2 CaM:peptide, confirmed by isothermal titration calorimetry, suggesting that each CaM domain independently binds one CK peptide in a Ca-depended manner. While the overall binding mode is similar between the structures with muscle or brain-type CK peptides, the most significant difference is the opposite binding orientation of the peptides in the N-terminal domain. This may extrapolate into distinct binding modes and regulation of the full-length CK isoforms. The structural insights gained in this study strengthen the link between cellular energy homeostasis and Ca-mediated cell signaling and may shed light on ways by which cells can 'fine tune' their energy levels to match the spatial and temporal demands.

PubMed: 34235492
DOI: 10.1016/j.crstbi.2021.05.001

Experimental method

X-RAY DIFFRACTION (1.24 Å)