2NA9

Transmembrane Structure of the P441A Mutant of the Cytokine Receptor Common Subunit beta

Summary for 2NA9

• Entry DOI: 10.2210/pdb2na9/pdb
• Related: 2na8
• NMR Information: BMRB: 25932
• Descriptor: Cytokine receptor common subunit beta (1 entity in total)
• Functional Keywords: transmembrane helix, nbp residue, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P32927
• Total number of polymer chains: 1
• Total formula weight: 5120.25

Authors

Schmidt, T.,Ye, F.,Situ, A.J.,An, W.,Ginsberg, M.H.,Ulmer, T.S. (deposition date: 2015-12-21, release date: 2016-07-06, Last modification date: 2024-05-15)

Primary citation

Schmidt, T.,Ye, F.,Situ, A.J.,An, W.,Ginsberg, M.H.,Ulmer, T.S.
A Conserved Ectodomain-Transmembrane Domain Linker Motif Tunes the Allosteric Regulation of Cell Surface Receptors.
J.Biol.Chem., 291:17536-17546, 2016

PubMed Abstract: In many families of cell surface receptors, a single transmembrane (TM) α-helix separates ecto- and cytosolic domains. A defined coupling of ecto- and TM domains must be essential to allosteric receptor regulation but remains little understood. Here, we characterize the linker structure, dynamics, and resulting ecto-TM domain coupling of integrin αIIb in model constructs and relate it to other integrin α subunits by mutagenesis. Cellular integrin activation assays subsequently validate the findings in intact receptors. Our results indicate a flexible yet carefully tuned ecto-TM coupling that modulates the signaling threshold of integrin receptors. Interestingly, a proline at the N-terminal TM helix border, termed NBP, is critical to linker flexibility in integrins. NBP is further predicted in 21% of human single-pass TM proteins and validated in cytokine receptors by the TM domain structure of the cytokine receptor common subunit β and its P441A-substituted variant. Thus, NBP is a conserved uncoupling motif of the ecto-TM domain transition and the degree of ecto-TM domain coupling represents an important parameter in the allosteric regulation of diverse cell surface receptors.

PubMed: 27365391
DOI: 10.1074/jbc.M116.733683

Experimental method

SOLUTION NMR