Limits...
Molecular modeling of the HAMP domain of sensory rhodopsin II transducer from Natronomonas pharaonis

View Article: PubMed Central - PubMed

ABSTRACT

The halobacterial transducer of sensory rhodopsin II (HtrII) is a photosignal transducer associated with phototaxis in extreme halophiles. The HAMP domain, a linker domain in HtrII, is considered to play an important role in transferring the signal from the membrane to the cytoplasmic region, although its structure in the complex remains undetermined. To establish the structural basis for understanding the mechanism of signal transduction, we present an atomic model of the structure of the N-terminal HAMP domain from Natronomonas pharaonis (HtrII: 84–136), based on molecular dynamics (MD) simulations. The model was built by homology modeling using the NMR structure of Af1503 from Archaeoglobus fulgidus as a template. The HAMP domains of Af1503 and HtrII were stable during MD simulations over 100 ns. Quantitative analyses of inter-helical packing indicated that the Af1503 HAMP domain stably maintained unusual knobs-to-knobs packing, as observed in the NMR structure, while the bulky side-chains of HtrII shifted the packing state to canonical knobs-into-holes. The role of the connector loop in maintaining structural stability was also discussed using MD simulations of loop deletion mutants.

No MeSH data available.


Related in: MedlinePlus

Inter-helical distances, defined by the distances between two helical axes, averaged for the last 50 ns of the simulations: Af1503 (red) and HtrII (black). The residue numbers shown are for Af1503 and are according to the alignment shown in Fig. 1. Vertical arrows indicate the locations of F124 and M127. Four different values of the average inter-helical distances are shown: (a) AS1(chain A)-AS1(chain B) and AS2(chain A)-AS2(chain B); (b) AS1(chain A)-AS2(chain A) (intra-chain; upper two curves) and AS1(A)-AS2(B) (inter-chain; lower two curves). In (b), the residue numbers are those of AS1.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC5036668&req=5

f8-6_27: Inter-helical distances, defined by the distances between two helical axes, averaged for the last 50 ns of the simulations: Af1503 (red) and HtrII (black). The residue numbers shown are for Af1503 and are according to the alignment shown in Fig. 1. Vertical arrows indicate the locations of F124 and M127. Four different values of the average inter-helical distances are shown: (a) AS1(chain A)-AS1(chain B) and AS2(chain A)-AS2(chain B); (b) AS1(chain A)-AS2(chain A) (intra-chain; upper two curves) and AS1(A)-AS2(B) (inter-chain; lower two curves). In (b), the residue numbers are those of AS1.

Mentions: The key residues determining packing form in HtrII are F124 and M127 (corresponding to Af1503 residues I319 and L322, respectively). These amino acids significantly increase the bulkiness of the side-chains in the packing core region (Fig. 6). These amino acid changes cause an increase in the distance between the AS2 helix in chain A and the AS2 helix in chain B on which F124 and M127 are located. Concurrently, the intra-chain distance between AS1(chain A) and AS2(chain A) was largely increased (Fig. 8). However, the inter-chain distance between AS1(chain A) and AS2(chain B) was maintained, or even decreased. The side-chain packing in knobs-to-knobs is stabilized mainly by x-x contacts between AS1(chain A) and AS1(chain B) or between AS2(chain A) and AS2(chain B), and the intra-chain x-da contacts between AS1(chain A) and AS2(chain A). The side-chain packing in the knobs-into-holes form is stabilized primarily by inter-helical a-d contacts between AS1(chain A) and AS2(chain B). Therefore, we conclude that the changes in the distances associated with F124 and M127 (Fig. 6) destabilize the packing of the knobs-to-knobs form, and induce the knobs-into-holes packing form.


Molecular modeling of the HAMP domain of sensory rhodopsin II transducer from Natronomonas pharaonis
Inter-helical distances, defined by the distances between two helical axes, averaged for the last 50 ns of the simulations: Af1503 (red) and HtrII (black). The residue numbers shown are for Af1503 and are according to the alignment shown in Fig. 1. Vertical arrows indicate the locations of F124 and M127. Four different values of the average inter-helical distances are shown: (a) AS1(chain A)-AS1(chain B) and AS2(chain A)-AS2(chain B); (b) AS1(chain A)-AS2(chain A) (intra-chain; upper two curves) and AS1(A)-AS2(B) (inter-chain; lower two curves). In (b), the residue numbers are those of AS1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5036668&req=5

f8-6_27: Inter-helical distances, defined by the distances between two helical axes, averaged for the last 50 ns of the simulations: Af1503 (red) and HtrII (black). The residue numbers shown are for Af1503 and are according to the alignment shown in Fig. 1. Vertical arrows indicate the locations of F124 and M127. Four different values of the average inter-helical distances are shown: (a) AS1(chain A)-AS1(chain B) and AS2(chain A)-AS2(chain B); (b) AS1(chain A)-AS2(chain A) (intra-chain; upper two curves) and AS1(A)-AS2(B) (inter-chain; lower two curves). In (b), the residue numbers are those of AS1.
Mentions: The key residues determining packing form in HtrII are F124 and M127 (corresponding to Af1503 residues I319 and L322, respectively). These amino acids significantly increase the bulkiness of the side-chains in the packing core region (Fig. 6). These amino acid changes cause an increase in the distance between the AS2 helix in chain A and the AS2 helix in chain B on which F124 and M127 are located. Concurrently, the intra-chain distance between AS1(chain A) and AS2(chain A) was largely increased (Fig. 8). However, the inter-chain distance between AS1(chain A) and AS2(chain B) was maintained, or even decreased. The side-chain packing in knobs-to-knobs is stabilized mainly by x-x contacts between AS1(chain A) and AS1(chain B) or between AS2(chain A) and AS2(chain B), and the intra-chain x-da contacts between AS1(chain A) and AS2(chain A). The side-chain packing in the knobs-into-holes form is stabilized primarily by inter-helical a-d contacts between AS1(chain A) and AS2(chain B). Therefore, we conclude that the changes in the distances associated with F124 and M127 (Fig. 6) destabilize the packing of the knobs-to-knobs form, and induce the knobs-into-holes packing form.

View Article: PubMed Central - PubMed

ABSTRACT

The halobacterial transducer of sensory rhodopsin II (HtrII) is a photosignal transducer associated with phototaxis in extreme halophiles. The HAMP domain, a linker domain in HtrII, is considered to play an important role in transferring the signal from the membrane to the cytoplasmic region, although its structure in the complex remains undetermined. To establish the structural basis for understanding the mechanism of signal transduction, we present an atomic model of the structure of the N-terminal HAMP domain from Natronomonas pharaonis (HtrII: 84–136), based on molecular dynamics (MD) simulations. The model was built by homology modeling using the NMR structure of Af1503 from Archaeoglobus fulgidus as a template. The HAMP domains of Af1503 and HtrII were stable during MD simulations over 100 ns. Quantitative analyses of inter-helical packing indicated that the Af1503 HAMP domain stably maintained unusual knobs-to-knobs packing, as observed in the NMR structure, while the bulky side-chains of HtrII shifted the packing state to canonical knobs-into-holes. The role of the connector loop in maintaining structural stability was also discussed using MD simulations of loop deletion mutants.

No MeSH data available.


Related in: MedlinePlus