SEA-PHAGES | Pleckstrin homology-like domain protein

Link to this post \| posted 22 Apr, 2025 18:47
nic.vega	Atlantica gp25 (in PECAAN) is showing high-probability full-length hits to prokaryotic Pleckstrin homology (PH)-like domain proteins (e.g. 3HSA_D, Shewanella protein YP_926556.1, type example). Other HHPred hits with similar scores are to the same domain structure in eukaryotic proteins, where the class was originally identified (e.g. 2N23_A, TFIIH p62, canonical example of PH domain). There are dissimilarities in the lengths of some of the disordered regions between structural sub-domains, and identity is low, but conservation of the structure is much better than homology of the sequence. At 104 aa, Atlantica gp25 is similar in length to a known sub-group of bacterial PH domain proteins typified by 3HSA_D but is shorter than a previously identified group of phage-associated PH domain proteins (~180 aa). AlphaFold indicates the characteristic 7-strand beta "sandwich" core + C-terminal alpha helix of this protein class (pic attached). I'm not sure whether PH-like domain meets the criteria to be added as a call. While PH-like domain is a structural class, it is a fairly specific 3' structure, and there is a function associated - canonically these proteins associate with membranes (lipid binding) and assemble other proteins at their location (protein-protein interactions). What do you think? Xu et al. 2010. Bacterial Pleckstrin Homology Domains: A Prokaryotic Origin for the PH Domain, Journal of Molecular Biology 396(1): 31-46. https://doi.org/10.1016/j.jmb.2009.11.006 (https://www.sciencedirect.com/science/article/pii/S0022283609013576) 1.19Mb

Link to this post | posted 22 Apr, 2025 18:47

Atlantica gp25 (in PECAAN) is showing high-probability full-length hits to prokaryotic Pleckstrin homology (PH)-like domain proteins (e.g. 3HSA_D, Shewanella protein YP_926556.1, type example). Other HHPred hits with similar scores are to the same domain structure in eukaryotic proteins, where the class was originally identified (e.g. 2N23_A, TFIIH p62, canonical example of PH domain). There are dissimilarities in the lengths of some of the disordered regions between structural sub-domains, and identity is low, but conservation of the structure is much better than homology of the sequence. At 104 aa, Atlantica gp25 is similar in length to a known sub-group of bacterial PH domain proteins typified by 3HSA_D but is shorter than a previously identified group of phage-associated PH domain proteins (~180 aa). AlphaFold indicates the characteristic 7-strand beta "sandwich" core + C-terminal alpha helix of this protein class (pic attached).

I'm not sure whether PH-like domain meets the criteria to be added as a call. While PH-like domain is a structural class, it is a fairly specific 3' structure, and there is a function associated - canonically these proteins associate with membranes (lipid binding) and assemble other proteins at their location (protein-protein interactions). What do you think?

Xu et al. 2010. Bacterial Pleckstrin Homology Domains: A Prokaryotic Origin for the PH Domain,
Journal of Molecular Biology 396(1): 31-46. https://doi.org/10.1016/j.jmb.2009.11.006 (https://www.sciencedirect.com/science/article/pii/S0022283609013576)

Link to this post \| posted 20 May, 2025 18:36
stpage	I ran alpha fold and HHPRED and am not super-convinced. It's only a beta-alpha-beta so pretty small compared to the other structures. But, the closest match in both HHPRED and alphafold is to a bacterial PH domain. So, certainly PH-domain-like. See attachment. 1.45Mb

Link to this post \| posted 12 Jun, 2025 18:15
stpage	I think I would say in general that the pleskstrin-homology domains closely share a structure, but do not closely share sequence similarity nor function. So, not super useful annotation anyway. See: Mark A. Lemmon, Chapter 136 - Pleckstrin Homology (PH) Domains, Editor(s): Ralph A. Bradshaw, Edward A. Dennis, Handbook of Cell Signaling (Second Edition), Academic Press, 2010, Pages 1093-1101, ISBN 9780123741455, https://doi.org/10.1016/B978-0-12-374145-5.00136-4. (https://www.sciencedirect.com/science/article/pii/B9780123741455001364)

Link to this post | posted 12 Jun, 2025 18:15

stpage

I think I would say in general that the pleskstrin-homology domains closely share a structure, but do not closely share sequence similarity *nor function*. So, not super useful annotation anyway.
See:
Mark A. Lemmon,
Chapter 136 - Pleckstrin Homology (PH) Domains,
Editor(s): Ralph A. Bradshaw, Edward A. Dennis,
Handbook of Cell Signaling (Second Edition),
Academic Press,
2010,
Pages 1093-1101,
ISBN 9780123741455,
https://doi.org/10.1016/B978-0-12-374145-5.00136-4.
(https://www.sciencedirect.com/science/article/pii/B9780123741455001364)

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Pleckstrin homology-like domain protein