The molecular basis for the pH-dependent calcium affinity of the pattern recognition receptor langerin.

ABSTRACT: The C-type lectin receptor langerin plays a vital role in the mammalian defense against invading pathogens. Langerin requires a Ca²⁺ cofactor, the binding affinity of which is regulated by pH. Thus, Ca²⁺ is bound when langerin is on the membrane but released when langerin and its pathogen substrate traffic to the acidic endosome, allowing the substrate to be degraded. The change in pH is sensed by protonation of the allosteric pH sensor histidine H294. However, the mechanism by which Ca²⁺ is released from the buried binding site is not clear. We studied the structural consequences of protonating H294 by molecular dynamics simulations (total simulation time: about 120 μs) and Markov models. We discovered a relay mechanism in which a proton is moved into the

SUBMITTER: Joswig JO 

PROVIDER: S-EPMC8219899 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature