Unraveling evolutionary constraints: a heterogeneous conservation in dynamics of the titin Ig domains.
The giant protein titin, which comprises immunoglobulin (Ig) domains, acts as a bidirectional spring in muscle. The unfolding of Ig domains has been extensively studied, but their dynamics under native states have not been well-characterized. We performed molecular dynamics simulation on a single titin Ig domain and multi-domains. Mobile regions displaying concerted motions were identified. The dynamics of Ig domains are constrained by evolutionary pressures, in such a way that global dominant motion is conserved, yet different flexibilities within Ig domains and in linkers connecting neighbouring domains were observed. We explain these heterogeneous conserved dynamics in relation to sequence conservation across species and the sequence diversity among neighbouring Ig domains.
Lukman
Suryani
S
Department of Chemistry, University of Cambridge, Cambridge, UK.
Grant
Guy H
GH
Bui
Jennifer M
JM
D000595:Amino Acid Sequence; D064211:Connectin; D017124:Conserved Sequence; D019277:Entropy; D019143:Evolution, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry*; D011494:Protein Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases