INVESTIGADORES
MALCHIODI Emilio Luis
artículos
Título:
Variable dimerization of the Ly49A natural killer cell receptor results in differential engagement of its MHC class I ligand.
Autor/es:
DAM J, BABER J, GRISHAEV A, MALCHIODI EL, SCHUCK P, BAX A, MARIUZZA RA.
Revista:
JOURNAL OF MOLECULAR BIOLOGY
Editorial:
ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Referencias:
Año: 2006 vol. 362 p. 102 - 113
ISSN:
0022-2836
Resumen:
Natural killer (NK) cells play a vital role in the detection and elimination of virally infected and tumor cells. The Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I molecules on target cells. Previous crystal studies revealed that the Ly49A homodimer binds one MHC molecule in an asymmetric interaction, whereas the Ly49C homodimer binds  two MHC in a symmetrical fashion. Moreover, the bound receptors adopt distinctly different homodimeric forms: a "closed state" for Ly49A and an "open state" for Ly49C. Steric clashes between MHC molecules would preclude the closed Ly49A dimmer from engaging two MHC in the manner of the open Ly49C dimer. To determine whetherindividual Ly49 receptors can undergo a conformational switch enabling them to bind MHC in different ways, we carried out a solution NMR study of unbound Ly49A, aided by dipolar coupling technology. This study reveals that, in solution, unligated Ly49A adopts a symmetric, open-state, homodimer conformation similar to that seen previously for Ly49C. Hence, Ly49A can assume both closed and open states. To address whether the Ly49A dimer can bind two MHC molecules in solution, besides the binding of one MHC observed in the crystal, we carried out  analytical ultracentrifugation experiments. Velocity sedimentation demonstrates that the Ly49A dimer can engage two MHC molecules in solution, in agreement with NMR results showing that unbound Ly49A exists predominantly in the open state.