Three-dimensional structure of recombinant human muscle fatty acid-binding protein.

Zanotti, Giuseppe; Scapin, Giovanna; Spadon, Paola; Veerkamp, J.H.; Sacchettini, James C.

doi:10.1016/s0021-9258(19)36996-0

Cited by 154 publications

(54 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Purified protein was then dialyzed into a final solution (20 mM sodium phosphate, 120 mM NaCl, pH 7.4). 15 N isotopically labelled protein used for NMR experiments followed the same protocol except cells were grown in M9 minimal media with 15 N-ammonium chloride. 15 N-FABP7 was dialyzed into NMR buffer (20 mM sodium phosphate, pH 7.4) for all NMR experiments.…”

Section: Methodsmentioning

confidence: 99%

“…All spectra were collected at 25°C and referenced to sodium trimethylsilylpropanesulfonate (DSS). 1 H- 15 N HSQC spectra was collected with a 50 µM FABP7 concentration. Fatty acids were titrated into 50 µM FABP7 sample from a DMSO stock, to a maximum of 2.5% DMSO volume content.…”

Section: Methodsmentioning

confidence: 99%

“…Binding to specific ligands may change the conformation of the NLS and promote nuclear localization. X-ray crystal structures of FABPs bound to fatty acids reveal that the fatty acids maintain similar poses in the FABP7 beta-barrel with hydrogen bonds to R126 and Y128 (15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

Bodnariuc

Lenz

Renaud-Young

et al. 2021

Preprint

View full text Add to dashboard Cite

Members of the fatty acid binding protein (FABP) family function as intracellular transporters of long chain fatty acids and other hydrophobic molecules to different cellular compartments. Brain fatty acid binding protein (FABP7) exhibits ligand-directed differences in cellular transport behavior. For example, when FABP7 binds to docosahexaenoic acid (DHA), the complex relocates to the nucleus and influences transcriptional activity, whereas FABP7 bound with monosaturated fatty acids remain in the cytosol. We used a variety of biophysical techniques to enhance understanding of ligand-directed transport. Specifically, we examine how FABP7 binds to fatty acids, including saturated stearic acid (SA), monounsaturated oleic acid (OA), and polyunsaturated DHA. We find that at 37°C FABP7 has near equivalent binding affinities for the fatty acids, while at lower temperatures, FABP7 exhibits a preference for the unsaturated fatty acids. Therefore, nuclear localization of the FABP7-DHA complex cannot be explained by binding preferences. Using NMR spectroscopy and molecular dynamics simulations, we observe that DHA uniquely affects the portal region of FABP7, which could enhance the complex's nuclear localization. Mutations to purported critical binding residues (R126L and Y128F) have little effect on fatty acid binding, with molecular dynamics simulations revealing that the bound fatty acid can adopt binding poses that can accommodate the mutations.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

Bodnariuc

Lenz

Renaud-Young

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In humans, ten FABPs have been identified to exhibit unique patterns of tissue expression in the liver, intestinal, heart, adipocytes, epidermis, ileus, brain, myelin, testis and retinoblastoma cell lines, which are involved in active lipid metabolism (Furuhashi & Hotamisligil, 2008;Liu et al, 2008). Among them, crystal structures of hFABP1, hFABP3, hFABP4, hFABP5 and hFABP8 (myelin P2, hMYP2) complexed with PA have been determined (Zanotti et al, 1992;Hohoff et al, 1999;Marr et al, 2006;Majava et al, 2010;Sharma & Sharma, 2011). Since the amino-acid sequences of each FABP are diverse, it is expected that PA would be bound to each with a different binding conformation involving different residues; however, this has not yet been elucidated.…”

Section: Structural Comparison Of Pa Binding To Other Hfabpsmentioning

confidence: 99%

Crystal structure of human brain-type fatty acid-binding protein FABP7 complexed with palmitic acid

Nam

2021

Acta Cryst Sect D Struct Biol

View full text Add to dashboard Cite

The brain-type fatty acid-binding protein FABP7, which is expressed in astrocytes and neural progenitors, is a member of the intracellular lipid-binding protein family. This protein is not only involved in various cellular functions such as metabolism, inflammation and energy homeostasis, but also in diseases such as cognitive disorders and tumors. Structures of unsaturated fatty acids, such as oleic acid (OA) and docosahexaenoic acid (DHA), bound to FABP7 have been elucidated; however, structures of saturated fatty acids bound to FABP7 remain unknown. To better understand fatty acid recognition, here the crystal structure of human brain-type fatty acid-binding protein FABP7 complexed with palmitic acid (PA), a saturated fatty acid, is reported at a resolution of 1.6 Å. The PA bound to the fatty acid-binding pocket of FABP7 assumed a U-shaped conformation. The carboxylate moiety of PA interacted with Tyr129, Arg127 and, via a water bridge, with Arg107 and Thr54, whereas its aliphatic chain was stabilized by hydrophobic interactions with Met21, Leu24, Thr30, Thr37, Pro39, Phe58 and Asp77. Structural comparison showed that PA, OA and DHA exhibited unique binding conformations in the fatty acid-binding pocket, stabilized by distinct amino-acid interactions. The binding of PA to FABP7 exhibits a unique binding conformation when compared with other human FABPs (FABP3–FABP5 and FABP8) expressed in other tissues. Based on the crystal and fatty acid structures, it was suggested that PA, which prefers a linear form in nature, required a greater conformational change in its aliphatic chain to bind to the fatty acid-binding pocket in a U-shaped conformation, compared with the cis configurations of OA or DHA. This, together with the length of the aliphatic chain, was considered to be one of the factors determining the binding affinity of PA to FABP7. These results provide a better understanding of fatty acid recognition by FABP7 and expand the knowledge of the binding of PA to FABPs.

show abstract

“…The FA is completely enclosed by hydrophobic interactions with a single hydrogen bond between the carboxylate group and R104 (Figure 1D). This form of complete enclosure is common among fatty acid binding proteins (FABP) (Jones et al, 1988;Coe and Bernlohr, 1998;Sacchettini et al, 1989;Xu et al, 1993;Zanotti et al, 1992), although the curved FA conformation would appear to be less common. In Rv1364c the conformation appears to be stabilized by each end of the FA.…”

Section: The Pas Domainmentioning

confidence: 99%

Structural Characterization of the Multidomain Regulatory Protein Rv1364c from Mycobacterium tuberculosis

et al. 2011

View full text Add to dashboard Cite

The open reading frame rv1364c of Mycobacterium tuberculosis, which regulates the stress-dependent σ factor, σ(F), has been analyzed structurally and functionally. Rv1364c contains domains with sequence similarity to the RsbP/RsbW/RsbV regulatory system of the stress-response σ factor of Bacillus subtilis. Rv1364c contains, sequentially, a PAS domain (which shows sequence similarity to the PAS domain of the B. subtilis RsbP protein), an active phosphatase domain, a kinase (anti-σ(F) like) domain and a C-terminal anti-σ(F) antagonist like domain. The crystal structures of two PAS domain constructs (at 2.3 and 1.6 Å) and a phosphatase/kinase dual domain construct (at 2.6 Å) are described. The PAS domain is shown to bind palmitic acid but to have 100 times greater affinity for palmitoleic acid. The full-length protein can exist in solution as both monomer and dimer. We speculate that a switch between monomer and dimer, possibly resulting from fatty acid binding, affects the accessibility of the serine of the C-terminal, anti-σ(F) antagonist domain for dephosphorylation by the phosphatase domain thus indirectly altering the availability of σ(F).

show abstract

Three-dimensional structure of recombinant human muscle fatty acid-binding protein.

Cited by 154 publications

References 29 publications

Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids

Crystal structure of human brain-type fatty acid-binding protein FABP7 complexed with palmitic acid

Structural Characterization of the Multidomain Regulatory Protein Rv1364c from Mycobacterium tuberculosis

Contact Info

Product

Resources

About