Abstract:
:Pulmonary surfactant protein D (SP-D) is a glycoprotein from the collectin family that is a component of the lung surfactant system. It exhibits host defense and immune regulatory functions in addition to contributing to the homeostasis of the surfactant pool within the alveolar airspaces. It is known that the SP-D monomer forms trimers, which further associate into higher-order oligomers. However, the pathway and the interactions involved in the assembly of SP-D oligomers are not clearly understood. In the current study, a recombinant form of full-length human SP-D (rhSP-D) has been qualitatively and quantitatively studied by atomic force microscopy (AFM) and electrophoresis, with the aim to understand the conformational diversity and the determinants defining the oligomerization of the protein. The rhSP-D preparation studied is a mixture of trimers, hexamers, dodecamers and higher-order oligomeric species, with dodecamers accounting for more than 50% of the protein by mass. Similar structures were also found in hSP-D obtained from proteinosis patients, with the largest fuzzy-ball-like oligomers being more abundant in these samples. The proportion of dodecamer is increased under acidic conditions, accompanied by a conformational change into more compact configurations. Two hexamers appear to be the minimal necessary unit for dodecamer formation, with stabilization of the dodecamer occurring via non-covalent, ionic, and hydrophobic interactions between the individual N-terminal domains and the proximal area of the SP-D collagen stems.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Arroyo R,Martín-González A,Echaide M,Jain A,Brondyk WH,Rosenbaum J,Moreno-Herrero F,Pérez-Gil Jdoi
10.1016/j.jmb.2018.03.027subject
Has Abstractpub_date
2018-05-11 00:00:00pages
1495-1509issue
10eissn
0022-2836issn
1089-8638pii
S0022-2836(18)30178-5journal_volume
430pub_type
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