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RE-REFINEMENT OF INTEGRIN ALPHAXBETA2 ECTODOMAIN IN THE CLOSED/BENT CONFORMATION
Structural highlights
FunctionITAX_HUMAN Integrin alpha-X/beta-2 is a receptor for fibrinogen. It recognizes the sequence G-P-R in fibrinogen. It mediates cell-cell interaction during inflammatory responses. It is especially important in monocyte adhesion and chemotaxis. Publication Abstract from PubMedHigh-resolution crystal structures of the headpiece of lymphocyte function-associated antigen-1 (integrin alphaLbeta2) reveal how the alphaI domain interacts with its platform formed by the alpha-subunit beta-propeller and beta-subunit betaI domains. The alphaLbeta2 structures compared with alphaXbeta2 structures show that the alphaI domain, tethered through its N-linker and a disulfide to a stable beta-ribbon pillar near the center of the platform, can undergo remarkable pivoting and tilting motions that appear buffered by N-glycan decorations that differ between alphaL and alphaX subunits. Rerefined beta2 integrin structures reveal details including pyroglutamic acid at the beta2 N terminus and bending within the EGF1 domain. Allostery is relayed to the alphaI domain by an internal ligand that binds to a pocket at the interface between the beta-propeller and betaI domains. Marked differences between the alphaL and alphaX subunit beta-propeller domains concentrate near the binding pocket and alphaI domain interfaces. Remarkably, movement in allostery in the betaI domain of specificity determining loop 1 (SDL1) causes concerted movement of SDL2 and thereby tightens the binding pocket for the internal ligand. Leukocyte integrin alphaLbeta2 headpiece structures: The alphaI domain, the pocket for the internal ligand, and concerted movements of its loops.,Sen M, Springer TA Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):2940-5. doi:, 10.1073/pnas.1601379113. Epub 2016 Mar 2. PMID:26936951[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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